TY  - JOUR
AU  - Horishny, Volodymyr
AU  - Geronikaki, Athina
AU  - Kartsev, Victor
AU  - Matiychuk, Vasyl
AU  - Petrou, Anthi
AU  - Pogodin, Pavel
AU  - Poroikov, Vladimir
AU  - Papadopoulou, Theodora A
AU  - Vizirianakis, Ioannis S
AU  - Kostić, Marina
AU  - Ivanov, Marija
AU  - Soković, Marina
PY  - 2022
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC8839324
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4884
AB  - BACKGROUND Infectious diseases represent a significant global strain on public health security and impact on socio-economic stability all over the world. The increasing resistance to the current antimicrobial treatment has resulted in the crucial need for the discovery and development of novel entities for the infectious treatment with different modes of action that could target both sensitive and resistant strains. METHODS Compounds were synthesized using the classical organic chemistry methods. Prediction of biological activity spectra was carried out using PASS and PASS-based web applications. Pharmacophore modeling in LigandScout software was used for quantitative modeling of the antibacterial activity. Antimicrobial activity was evaluated using the microdilution method. AutoDock 4.2® software was used to elucidate probable bacterial and fungal molecular targets of the studied compounds. RESULTS All compounds exhibited better antibacterial potency than ampicillin against all bacteria tested. Three compounds were tested against resistant strains MRSA, P. aeruginosa and E. coli and were found to be more potent than MRSA than reference drugs. All compounds demonstrated a higher degree of antifungal activity than the reference drugs bifonazole (6-17-fold) and ketoconazole (13-52-fold). Three of the most active compounds could be considered for further development of the new, more potent antimicrobial agents. CONCLUSION Compounds 5b (Z)-3-(3-hydroxyphenyl)-5-((1-methyl-1H-indol-3-yl)methylene)-2-thioxothiazolidin-4-one and 5g (Z)-3-[5-(1H-Indol-3-ylmethylene)-4-oxo-2-thioxo-thiazolidin-3-yl]-benzoic acid as well as 5h (Z)-3-(5-((5-methoxy-1H-indol-3-yl)methylene)-4-oxo-2-thioxothiazolidin-3-yl)benzoic acid can be considered as lead compounds for further development of more potent and safe antibacterial and antifungal agents.
PB  - Basel: MDPI
T2  - Molecules
T1  - Synthesis, Biological Evaluation and Molecular Docking Studies of 5-Indolylmethylen-4-oxo-2-thioxothiazolidine Derivatives.
IS  - 3
VL  - 27
DO  - 10.3390/molecules27031068
SP  - 1068
ER  - 

@article{
author = "Horishny, Volodymyr and Geronikaki, Athina and Kartsev, Victor and Matiychuk, Vasyl and Petrou, Anthi and Pogodin, Pavel and Poroikov, Vladimir and Papadopoulou, Theodora A and Vizirianakis, Ioannis S and Kostić, Marina and Ivanov, Marija and Soković, Marina",
year = "2022",
abstract = "BACKGROUND Infectious diseases represent a significant global strain on public health security and impact on socio-economic stability all over the world. The increasing resistance to the current antimicrobial treatment has resulted in the crucial need for the discovery and development of novel entities for the infectious treatment with different modes of action that could target both sensitive and resistant strains. METHODS Compounds were synthesized using the classical organic chemistry methods. Prediction of biological activity spectra was carried out using PASS and PASS-based web applications. Pharmacophore modeling in LigandScout software was used for quantitative modeling of the antibacterial activity. Antimicrobial activity was evaluated using the microdilution method. AutoDock 4.2® software was used to elucidate probable bacterial and fungal molecular targets of the studied compounds. RESULTS All compounds exhibited better antibacterial potency than ampicillin against all bacteria tested. Three compounds were tested against resistant strains MRSA, P. aeruginosa and E. coli and were found to be more potent than MRSA than reference drugs. All compounds demonstrated a higher degree of antifungal activity than the reference drugs bifonazole (6-17-fold) and ketoconazole (13-52-fold). Three of the most active compounds could be considered for further development of the new, more potent antimicrobial agents. CONCLUSION Compounds 5b (Z)-3-(3-hydroxyphenyl)-5-((1-methyl-1H-indol-3-yl)methylene)-2-thioxothiazolidin-4-one and 5g (Z)-3-[5-(1H-Indol-3-ylmethylene)-4-oxo-2-thioxo-thiazolidin-3-yl]-benzoic acid as well as 5h (Z)-3-(5-((5-methoxy-1H-indol-3-yl)methylene)-4-oxo-2-thioxothiazolidin-3-yl)benzoic acid can be considered as lead compounds for further development of more potent and safe antibacterial and antifungal agents.",
publisher = "Basel: MDPI",
journal = "Molecules",
title = "Synthesis, Biological Evaluation and Molecular Docking Studies of 5-Indolylmethylen-4-oxo-2-thioxothiazolidine Derivatives.",
number = "3",
volume = "27",
doi = "10.3390/molecules27031068",
pages = "1068"
}

Horishny, V., Geronikaki, A., Kartsev, V., Matiychuk, V., Petrou, A., Pogodin, P., Poroikov, V., Papadopoulou, T. A., Vizirianakis, I. S., Kostić, M., Ivanov, M.,& Soković, M.. (2022). Synthesis, Biological Evaluation and Molecular Docking Studies of 5-Indolylmethylen-4-oxo-2-thioxothiazolidine Derivatives.. in Molecules
Basel: MDPI., 27(3), 1068.
https://doi.org/10.3390/molecules27031068

Horishny V, Geronikaki A, Kartsev V, Matiychuk V, Petrou A, Pogodin P, Poroikov V, Papadopoulou TA, Vizirianakis IS, Kostić M, Ivanov M, Soković M. Synthesis, Biological Evaluation and Molecular Docking Studies of 5-Indolylmethylen-4-oxo-2-thioxothiazolidine Derivatives.. in Molecules. 2022;27(3):1068.
doi:10.3390/molecules27031068 .

Horishny, Volodymyr, Geronikaki, Athina, Kartsev, Victor, Matiychuk, Vasyl, Petrou, Anthi, Pogodin, Pavel, Poroikov, Vladimir, Papadopoulou, Theodora A, Vizirianakis, Ioannis S, Kostić, Marina, Ivanov, Marija, Soković, Marina, "Synthesis, Biological Evaluation and Molecular Docking Studies of 5-Indolylmethylen-4-oxo-2-thioxothiazolidine Derivatives." in Molecules, 27, no. 3 (2022):1068,
https://doi.org/10.3390/molecules27031068 . .

TY  - JOUR
AU  - Kamoutsis, Charalampos
AU  - Fesatidou, Maria
AU  - Petrou, Anthi
AU  - Geronikaki, Athina
AU  - Poroikov, Vladimir
AU  - Ivanov, Marija
AU  - Soković, Marina
AU  - Ćirić, Ana
AU  - Carazo, Alejandro
AU  - Mladenka, Premysl
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4298
AB  - The goal of this research is to investigate the antimicrobial activity of nineteen previously
synthesized 3,6-disubstituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives. The compounds were
tested against a panel of three Gram-positive and three Gram-negative bacteria, three resistant strains,
and six fungi. Minimal inhibitory, bactericidal, and fungicidal concentrations were determined by a
microdilution method. All of the compounds showed antibacterial activity that was more potent
than both reference drugs, ampicillin and streptomycin, against all bacteria tested. Similarly, they
were also more active against resistant bacterial strains. The antifungal activity of the compounds
was up to 80-fold higher than ketoconazole and from 3 to 40 times higher than bifonazole, both of
which were used as reference drugs. The most active compounds (2, 3, 6, 7, and 19) were tested for
their inhibition of P. aeruginosa biofilm formation. Among them, compound 3 showed significantly
higher antibiofilm activity and appeared to be equipotent with ampicillin. The prediction of the
probable mechanism by docking on antibacterial targets revealed that E. coli MurB is the most suitable
enzyme, while docking studies on antifungal targets indicated a probable involvement of CYP51 in
the mechanism of antifungal activity. Finally, the toxicity testing in human cells confirmed their low
toxicity both in cancerous cell line MCF7 and non-cancerous cell line HK-2.
PB  - MDPI
T2  - Antibiotics
T1  - Triazolo Based-Thiadiazole Derivatives. Synthesis, Biological Evaluation and Molecular Docking Studies
IS  - 7
VL  - 10
DO  - 10.3390/antibiotics10070804
SP  - 804
ER  - 

@article{
author = "Kamoutsis, Charalampos and Fesatidou, Maria and Petrou, Anthi and Geronikaki, Athina and Poroikov, Vladimir and Ivanov, Marija and Soković, Marina and Ćirić, Ana and Carazo, Alejandro and Mladenka, Premysl",
year = "2021",
abstract = "The goal of this research is to investigate the antimicrobial activity of nineteen previously
synthesized 3,6-disubstituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives. The compounds were
tested against a panel of three Gram-positive and three Gram-negative bacteria, three resistant strains,
and six fungi. Minimal inhibitory, bactericidal, and fungicidal concentrations were determined by a
microdilution method. All of the compounds showed antibacterial activity that was more potent
than both reference drugs, ampicillin and streptomycin, against all bacteria tested. Similarly, they
were also more active against resistant bacterial strains. The antifungal activity of the compounds
was up to 80-fold higher than ketoconazole and from 3 to 40 times higher than bifonazole, both of
which were used as reference drugs. The most active compounds (2, 3, 6, 7, and 19) were tested for
their inhibition of P. aeruginosa biofilm formation. Among them, compound 3 showed significantly
higher antibiofilm activity and appeared to be equipotent with ampicillin. The prediction of the
probable mechanism by docking on antibacterial targets revealed that E. coli MurB is the most suitable
enzyme, while docking studies on antifungal targets indicated a probable involvement of CYP51 in
the mechanism of antifungal activity. Finally, the toxicity testing in human cells confirmed their low
toxicity both in cancerous cell line MCF7 and non-cancerous cell line HK-2.",
publisher = "MDPI",
journal = "Antibiotics",
title = "Triazolo Based-Thiadiazole Derivatives. Synthesis, Biological Evaluation and Molecular Docking Studies",
number = "7",
volume = "10",
doi = "10.3390/antibiotics10070804",
pages = "804"
}

Kamoutsis, C., Fesatidou, M., Petrou, A., Geronikaki, A., Poroikov, V., Ivanov, M., Soković, M., Ćirić, A., Carazo, A.,& Mladenka, P.. (2021). Triazolo Based-Thiadiazole Derivatives. Synthesis, Biological Evaluation and Molecular Docking Studies. in Antibiotics
MDPI., 10(7), 804.
https://doi.org/10.3390/antibiotics10070804

Kamoutsis C, Fesatidou M, Petrou A, Geronikaki A, Poroikov V, Ivanov M, Soković M, Ćirić A, Carazo A, Mladenka P. Triazolo Based-Thiadiazole Derivatives. Synthesis, Biological Evaluation and Molecular Docking Studies. in Antibiotics. 2021;10(7):804.
doi:10.3390/antibiotics10070804 .

Kamoutsis, Charalampos, Fesatidou, Maria, Petrou, Anthi, Geronikaki, Athina, Poroikov, Vladimir, Ivanov, Marija, Soković, Marina, Ćirić, Ana, Carazo, Alejandro, Mladenka, Premysl, "Triazolo Based-Thiadiazole Derivatives. Synthesis, Biological Evaluation and Molecular Docking Studies" in Antibiotics, 10, no. 7 (2021):804,
https://doi.org/10.3390/antibiotics10070804 . .

TY  - JOUR
AU  - Zveaghintseva, Marina
AU  - Stingaci, Eugenia
AU  - Pogrebnoi, Sergei
AU  - Smetanscaia, Anastasia
AU  - Valica, Vladimir
AU  - Uncu, Livia
AU  - Kravtsov, Victor
AU  - Melnik, Elena
AU  - Petrou, Anthi
AU  - Glamočlija, Jasmina
AU  - Soković, Marina
AU  - Carazo, Alejandro
AU  - Mladěnka, Přemysl
AU  - Poroikov, Vladimir
AU  - Geronikaki, Athina
AU  - Macaev, Fliur
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4305
AB  - Herein we report the synthesis of some new 1H-1,2,4-triazole functionalized chromenols
(3a–3n) via tandem reactions of 1-(alkyl/aryl)-2-(1H-1,2,4-triazole-1-yl) with salicylic aldehydes and
the evaluation of their antifungal activity. In silico prediction of biological activity spectra with
computer program PASS indicate that the compounds have a high novelty compared to the known
antifungal agents. We did not find any close analog among the over 580,000 pharmaceutical agents
in the Cortellis Drug Discovery Intelligence database at the similarity cutoff of 70%. The evaluation
of antifungal activity in vitro revealed that the highest activity was exhibited by compound 3k,
followed by 3n. Their MIC values for different fungi were 22.1–184.2 and 71.3–199.8  M, respectively.
Twelve from fourteen tested compounds were more active than the reference drugs ketoconazole and
bifonazole. The most sensitive fungus appeared to be Trichoderma viride, while Aspergillus fumigatus
was the most resistant one. It was found that the presence of the 2-(tert-butyl)-2H-chromen-2-ol
substituent on the 4th position of the triazole ring is very beneficial for antifungal activity. Molecular
docking studies on C. albicans sterol 14 -demethylase (CYP51) and DNA topoisomerase IV were used
to predict the mechanism of antifungal activities. According to the docking results, the inhibition
of CYP51 is a putative mechanism of antifungal activity of the novel chromenol derivatives. We
also showed that most active compounds have a low cytotoxicity, which allows us to consider them
promising antifungal agents for the subsequent testing activity in in vivo assays.
PB  - Basel: MDPI
T2  - Molecules
T1  - Chromenol Derivatives as Novel Antifungal Agents: Synthesis, In Silico and In Vitro Evaluation
IS  - 14
VL  - 26
DO  - 10.3390/molecules26144304
SP  - 4304
ER  - 

@article{
author = "Zveaghintseva, Marina and Stingaci, Eugenia and Pogrebnoi, Sergei and Smetanscaia, Anastasia and Valica, Vladimir and Uncu, Livia and Kravtsov, Victor and Melnik, Elena and Petrou, Anthi and Glamočlija, Jasmina and Soković, Marina and Carazo, Alejandro and Mladěnka, Přemysl and Poroikov, Vladimir and Geronikaki, Athina and Macaev, Fliur",
year = "2021",
abstract = "Herein we report the synthesis of some new 1H-1,2,4-triazole functionalized chromenols
(3a–3n) via tandem reactions of 1-(alkyl/aryl)-2-(1H-1,2,4-triazole-1-yl) with salicylic aldehydes and
the evaluation of their antifungal activity. In silico prediction of biological activity spectra with
computer program PASS indicate that the compounds have a high novelty compared to the known
antifungal agents. We did not find any close analog among the over 580,000 pharmaceutical agents
in the Cortellis Drug Discovery Intelligence database at the similarity cutoff of 70%. The evaluation
of antifungal activity in vitro revealed that the highest activity was exhibited by compound 3k,
followed by 3n. Their MIC values for different fungi were 22.1–184.2 and 71.3–199.8  M, respectively.
Twelve from fourteen tested compounds were more active than the reference drugs ketoconazole and
bifonazole. The most sensitive fungus appeared to be Trichoderma viride, while Aspergillus fumigatus
was the most resistant one. It was found that the presence of the 2-(tert-butyl)-2H-chromen-2-ol
substituent on the 4th position of the triazole ring is very beneficial for antifungal activity. Molecular
docking studies on C. albicans sterol 14 -demethylase (CYP51) and DNA topoisomerase IV were used
to predict the mechanism of antifungal activities. According to the docking results, the inhibition
of CYP51 is a putative mechanism of antifungal activity of the novel chromenol derivatives. We
also showed that most active compounds have a low cytotoxicity, which allows us to consider them
promising antifungal agents for the subsequent testing activity in in vivo assays.",
publisher = "Basel: MDPI",
journal = "Molecules",
title = "Chromenol Derivatives as Novel Antifungal Agents: Synthesis, In Silico and In Vitro Evaluation",
number = "14",
volume = "26",
doi = "10.3390/molecules26144304",
pages = "4304"
}

Zveaghintseva, M., Stingaci, E., Pogrebnoi, S., Smetanscaia, A., Valica, V., Uncu, L., Kravtsov, V., Melnik, E., Petrou, A., Glamočlija, J., Soković, M., Carazo, A., Mladěnka, P., Poroikov, V., Geronikaki, A.,& Macaev, F.. (2021). Chromenol Derivatives as Novel Antifungal Agents: Synthesis, In Silico and In Vitro Evaluation. in Molecules
Basel: MDPI., 26(14), 4304.
https://doi.org/10.3390/molecules26144304

Zveaghintseva M, Stingaci E, Pogrebnoi S, Smetanscaia A, Valica V, Uncu L, Kravtsov V, Melnik E, Petrou A, Glamočlija J, Soković M, Carazo A, Mladěnka P, Poroikov V, Geronikaki A, Macaev F. Chromenol Derivatives as Novel Antifungal Agents: Synthesis, In Silico and In Vitro Evaluation. in Molecules. 2021;26(14):4304.
doi:10.3390/molecules26144304 .

Zveaghintseva, Marina, Stingaci, Eugenia, Pogrebnoi, Sergei, Smetanscaia, Anastasia, Valica, Vladimir, Uncu, Livia, Kravtsov, Victor, Melnik, Elena, Petrou, Anthi, Glamočlija, Jasmina, Soković, Marina, Carazo, Alejandro, Mladěnka, Přemysl, Poroikov, Vladimir, Geronikaki, Athina, Macaev, Fliur, "Chromenol Derivatives as Novel Antifungal Agents: Synthesis, In Silico and In Vitro Evaluation" in Molecules, 26, no. 14 (2021):4304,
https://doi.org/10.3390/molecules26144304 . .

TY  - JOUR
AU  - Horishny, Volodymyr
AU  - Kartsev, Victor
AU  - Matiychuk, Vasyl
AU  - Geronikaki, Athina
AU  - Anthi, Petrou
AU  - Pogodin, Pavel
AU  - Poroikov, Vladimir
AU  - Ivanov, Marija
AU  - Kostić, Marina
AU  - Soković, Marina
AU  - Eleftheriou, Phaedra
PY  - 2020
UR  - https://www.mdpi.com/1424-8247/13/9/229
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3942
AB  - Herein we report the design, synthesis, computational, and experimental evaluation of the antimicrobial activity of fourteen new 3-amino-5-(indol-3-yl) methylene-4-oxo-2-thioxothiazolidine derivatives. The structures were designed, and their antimicrobial activity and toxicity were predicted in silico. All synthesized compounds exhibited antibacterial activity against eight Gram-positive and Gram-negative bacteria. Their activity exceeded those of ampicillin and (for the majority of compounds) streptomycin. The most sensitive bacterium was S. aureus (American Type Culture Collection ATCC 6538), while L. monocytogenes (NCTC 7973) was the most resistant. The best antibacterial activity was observed for compound 5d (Z)-N-(5-((1H-indol-3-yl)methylene)-4-oxo-2-thioxothiazolidin-3-yl)-4-hydroxybenzamide (Minimal inhibitory concentration, MIC at 37.9–113.8 μM, and Minimal bactericidal concentration MBC at 57.8–118.3 μM). Three most active compounds 5d, 5g, and 5k being evaluated against three resistant strains, Methicillin resistant Staphilococcus aureus (MRSA), P. aeruginosa, and E. coli, were more potent against MRSA than ampicillin (MIC at 248–372 μM, MBC at 372–1240 μM). At the same time, streptomycin (MIC at 43–172 μM, MBC at 86–344 μM) did not show bactericidal activity at all. The compound 5d was also more active than ampicillin towards resistant P. aeruginosa strain. Antifungal activity of all compounds exceeded those of the reference antifungal agents bifonazole (MIC at 480–640 μM, and MFC at 640–800 μM) and ketoconazole (MIC 285–475 μM and MFC 380–950 μM). The best activity was exhibited by compound 5g. The most sensitive fungal was T. viride (IAM 5061), while A. fumigatus (human isolate) was the most resistant. Low cytotoxicity against HEK-293 human embryonic kidney cell line and reasonable selectivity indices were shown for the most active compounds 5d, 5g, 5k, 7c using thiazolyl blue tetrazolium bromide MTT assay. The docking studies indicated a probable involvement of E. coli Mur B inhibition in the antibacterial action, while CYP51 inhibition is likely responsible for the antifungal activity of the tested compounds.
PB  - MDPI AG
T2  - Pharmaceuticals
T1  - 3-Amino-5-(indol-3-yl)methylene-4-oxo-2-thioxothiazolidine Derivatives as Antimicrobial Agents: Synthesis, Computational and Biological Evaluation
IS  - 9
VL  - 13
DO  - 10.3390/ph13090229
SP  - 229
ER  - 

@article{
author = "Horishny, Volodymyr and Kartsev, Victor and Matiychuk, Vasyl and Geronikaki, Athina and Anthi, Petrou and Pogodin, Pavel and Poroikov, Vladimir and Ivanov, Marija and Kostić, Marina and Soković, Marina and Eleftheriou, Phaedra",
year = "2020",
abstract = "Herein we report the design, synthesis, computational, and experimental evaluation of the antimicrobial activity of fourteen new 3-amino-5-(indol-3-yl) methylene-4-oxo-2-thioxothiazolidine derivatives. The structures were designed, and their antimicrobial activity and toxicity were predicted in silico. All synthesized compounds exhibited antibacterial activity against eight Gram-positive and Gram-negative bacteria. Their activity exceeded those of ampicillin and (for the majority of compounds) streptomycin. The most sensitive bacterium was S. aureus (American Type Culture Collection ATCC 6538), while L. monocytogenes (NCTC 7973) was the most resistant. The best antibacterial activity was observed for compound 5d (Z)-N-(5-((1H-indol-3-yl)methylene)-4-oxo-2-thioxothiazolidin-3-yl)-4-hydroxybenzamide (Minimal inhibitory concentration, MIC at 37.9–113.8 μM, and Minimal bactericidal concentration MBC at 57.8–118.3 μM). Three most active compounds 5d, 5g, and 5k being evaluated against three resistant strains, Methicillin resistant Staphilococcus aureus (MRSA), P. aeruginosa, and E. coli, were more potent against MRSA than ampicillin (MIC at 248–372 μM, MBC at 372–1240 μM). At the same time, streptomycin (MIC at 43–172 μM, MBC at 86–344 μM) did not show bactericidal activity at all. The compound 5d was also more active than ampicillin towards resistant P. aeruginosa strain. Antifungal activity of all compounds exceeded those of the reference antifungal agents bifonazole (MIC at 480–640 μM, and MFC at 640–800 μM) and ketoconazole (MIC 285–475 μM and MFC 380–950 μM). The best activity was exhibited by compound 5g. The most sensitive fungal was T. viride (IAM 5061), while A. fumigatus (human isolate) was the most resistant. Low cytotoxicity against HEK-293 human embryonic kidney cell line and reasonable selectivity indices were shown for the most active compounds 5d, 5g, 5k, 7c using thiazolyl blue tetrazolium bromide MTT assay. The docking studies indicated a probable involvement of E. coli Mur B inhibition in the antibacterial action, while CYP51 inhibition is likely responsible for the antifungal activity of the tested compounds.",
publisher = "MDPI AG",
journal = "Pharmaceuticals",
title = "3-Amino-5-(indol-3-yl)methylene-4-oxo-2-thioxothiazolidine Derivatives as Antimicrobial Agents: Synthesis, Computational and Biological Evaluation",
number = "9",
volume = "13",
doi = "10.3390/ph13090229",
pages = "229"
}

Horishny, V., Kartsev, V., Matiychuk, V., Geronikaki, A., Anthi, P., Pogodin, P., Poroikov, V., Ivanov, M., Kostić, M., Soković, M.,& Eleftheriou, P.. (2020). 3-Amino-5-(indol-3-yl)methylene-4-oxo-2-thioxothiazolidine Derivatives as Antimicrobial Agents: Synthesis, Computational and Biological Evaluation. in Pharmaceuticals
MDPI AG., 13(9), 229.
https://doi.org/10.3390/ph13090229

Horishny V, Kartsev V, Matiychuk V, Geronikaki A, Anthi P, Pogodin P, Poroikov V, Ivanov M, Kostić M, Soković M, Eleftheriou P. 3-Amino-5-(indol-3-yl)methylene-4-oxo-2-thioxothiazolidine Derivatives as Antimicrobial Agents: Synthesis, Computational and Biological Evaluation. in Pharmaceuticals. 2020;13(9):229.
doi:10.3390/ph13090229 .

Horishny, Volodymyr, Kartsev, Victor, Matiychuk, Vasyl, Geronikaki, Athina, Anthi, Petrou, Pogodin, Pavel, Poroikov, Vladimir, Ivanov, Marija, Kostić, Marina, Soković, Marina, Eleftheriou, Phaedra, "3-Amino-5-(indol-3-yl)methylene-4-oxo-2-thioxothiazolidine Derivatives as Antimicrobial Agents: Synthesis, Computational and Biological Evaluation" in Pharmaceuticals, 13, no. 9 (2020):229,
https://doi.org/10.3390/ph13090229 . .

TY  - JOUR
AU  - Amiranashvili, Lela
AU  - Nadaraia, Nanuli
AU  - Merlani, Maia
AU  - Kamoutsis, Charalampos
AU  - Petrou, Anthi
AU  - Geronikaki, Athina
AU  - Pogodin, Pavel
AU  - Druzhilovskiy, Dmitry
AU  - Poroikov, Vladimir
AU  - Ćirić, Ana
AU  - Glamočlija, Jasmina
AU  - Soković, Marina
PY  - 2020
UR  - https://www.mdpi.com/2079-6382/9/5/224
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC7277561
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3691
AB  - We evaluated the antimicrobial activity of thirty-one nitrogen-containing 5-alpha-androstane derivatives in silico using computer program PASS (Prediction of Activity Spectra for Substances) and freely available PASS-based web applications (www.way2drug.com). Antibacterial activity was predicted for 27 out of 31 molecules; antifungal activity was predicted for 25 out of 31 compounds. The results of experiments, which we conducted to study the antimicrobial activity, are in agreement with the predictions. All compounds were found to be active with MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration) values in the range of 0.0005-0.6 mg/mL. The activity of all studied 5-alpha-androstane derivatives exceeded or was equal to those of Streptomycin and, except for the 3β-hydroxy-17α-aza-d-homo-5α-androstane-17-one, all molecules were more active than Ampicillin. Activity against the resistant strains of E. coli,P. aeruginosa, and methicillin-resistant Staphylococcus aureus was also shown in experiments. Antifungal activity was determined with MIC and MFC (Minimum Fungicidal Concentration) values varying from 0.007 to 0.6 mg/mL. Most of the compounds were found to be more potent than the reference drugs Bifonazole and Ketoconazole. According to the results of docking studies, the putative targets for antibacterial and antifungal activity are UDP-N-acetylenolpyruvoylglucosamine reductase and 14-alpha demethylase, respectively. In silico assessments of the acute rodent toxicity and cytotoxicity obtained using GUSAR (General Unrestricted Structure-Activity Relationships) and CLC-Pred (Cell Line Cytotoxicity Predictor) web-services were low for the majority of compounds under study, which contributes to the chances for those compounds to advance in the development.
PB  - MDPI AG
T2  - Antibiotics (Basel, Switzerland)
T1  - Antimicrobial Activity of Nitrogen-Containing 5-Alpha-androstane Derivatives: In Silico and Experimental Studies.
IS  - 5
VL  - 9
DO  - 10.3390/antibiotics9050224
SP  - 224
ER  - 

@article{
author = "Amiranashvili, Lela and Nadaraia, Nanuli and Merlani, Maia and Kamoutsis, Charalampos and Petrou, Anthi and Geronikaki, Athina and Pogodin, Pavel and Druzhilovskiy, Dmitry and Poroikov, Vladimir and Ćirić, Ana and Glamočlija, Jasmina and Soković, Marina",
year = "2020",
abstract = "We evaluated the antimicrobial activity of thirty-one nitrogen-containing 5-alpha-androstane derivatives in silico using computer program PASS (Prediction of Activity Spectra for Substances) and freely available PASS-based web applications (www.way2drug.com). Antibacterial activity was predicted for 27 out of 31 molecules; antifungal activity was predicted for 25 out of 31 compounds. The results of experiments, which we conducted to study the antimicrobial activity, are in agreement with the predictions. All compounds were found to be active with MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration) values in the range of 0.0005-0.6 mg/mL. The activity of all studied 5-alpha-androstane derivatives exceeded or was equal to those of Streptomycin and, except for the 3β-hydroxy-17α-aza-d-homo-5α-androstane-17-one, all molecules were more active than Ampicillin. Activity against the resistant strains of E. coli,P. aeruginosa, and methicillin-resistant Staphylococcus aureus was also shown in experiments. Antifungal activity was determined with MIC and MFC (Minimum Fungicidal Concentration) values varying from 0.007 to 0.6 mg/mL. Most of the compounds were found to be more potent than the reference drugs Bifonazole and Ketoconazole. According to the results of docking studies, the putative targets for antibacterial and antifungal activity are UDP-N-acetylenolpyruvoylglucosamine reductase and 14-alpha demethylase, respectively. In silico assessments of the acute rodent toxicity and cytotoxicity obtained using GUSAR (General Unrestricted Structure-Activity Relationships) and CLC-Pred (Cell Line Cytotoxicity Predictor) web-services were low for the majority of compounds under study, which contributes to the chances for those compounds to advance in the development.",
publisher = "MDPI AG",
journal = "Antibiotics (Basel, Switzerland)",
title = "Antimicrobial Activity of Nitrogen-Containing 5-Alpha-androstane Derivatives: In Silico and Experimental Studies.",
number = "5",
volume = "9",
doi = "10.3390/antibiotics9050224",
pages = "224"
}

Amiranashvili, L., Nadaraia, N., Merlani, M., Kamoutsis, C., Petrou, A., Geronikaki, A., Pogodin, P., Druzhilovskiy, D., Poroikov, V., Ćirić, A., Glamočlija, J.,& Soković, M.. (2020). Antimicrobial Activity of Nitrogen-Containing 5-Alpha-androstane Derivatives: In Silico and Experimental Studies.. in Antibiotics (Basel, Switzerland)
MDPI AG., 9(5), 224.
https://doi.org/10.3390/antibiotics9050224

Amiranashvili L, Nadaraia N, Merlani M, Kamoutsis C, Petrou A, Geronikaki A, Pogodin P, Druzhilovskiy D, Poroikov V, Ćirić A, Glamočlija J, Soković M. Antimicrobial Activity of Nitrogen-Containing 5-Alpha-androstane Derivatives: In Silico and Experimental Studies.. in Antibiotics (Basel, Switzerland). 2020;9(5):224.
doi:10.3390/antibiotics9050224 .

Amiranashvili, Lela, Nadaraia, Nanuli, Merlani, Maia, Kamoutsis, Charalampos, Petrou, Anthi, Geronikaki, Athina, Pogodin, Pavel, Druzhilovskiy, Dmitry, Poroikov, Vladimir, Ćirić, Ana, Glamočlija, Jasmina, Soković, Marina, "Antimicrobial Activity of Nitrogen-Containing 5-Alpha-androstane Derivatives: In Silico and Experimental Studies." in Antibiotics (Basel, Switzerland), 9, no. 5 (2020):224,
https://doi.org/10.3390/antibiotics9050224 . .

TY  - JOUR
AU  - Merlani, Maia
AU  - Barbakadze, Vakhtang
AU  - Amiranashvili, Lela
AU  - Gogilashvili, Lali
AU  - Poroikov, Vladimir
AU  - Petrou, Anthi
AU  - Geronikaki, Athina
AU  - Ćirić, Ana
AU  - Glamočlija, Jasmina
AU  - Soković, Marina
PY  - 2019
UR  - http://www.eurekaselect.com/169251/article
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3346
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3411
AB  - BACKGROUND Phenolic acids (caffeic-, ferulic and p-coumaric acid) are widely distributed in the plant kingdom and exhibit broad spectrum of biological activities, including antimicrobial activity. OBJECTIVE The goal of this paper is the synthesis of some caffeic acid derivatives selected based on computer-aided predictions and evaluate their in vitro antimicrobial properties against Gram positive and Gram negative bacteria and also a series of fungi. METHODS In silico prediction of biological activity was used to identify the most promising structures for synthesis and biological testing, and the putative mechanisms of their antimicrobial action. The designed compounds were synthesized using classical organic synthesis methods. The antimicrobial activity was studied using microdilution method. RESULTS Twelve tested compounds have shown good antibacterial activity. Five out of twelve tested compounds appeared to be more active than the reference drugs ampicillin and streptomycin. Despite that all compounds exhibited good activity against all bacteria tested, the sensitivity of bacteria towards compounds in general was different. The evaluation of antifungal activity revealed that all compounds were more active than ketoconazole, while seven compounds (2, 3, 4, 5, 7, 8 and 12) appeared to be more active than bifonazole. Docking results indicate that gyrase inhibition is the putative mechanism of antibacterial action while the inhibition of 14α-demethylase may be responsible for antifungal action. Prediction of cytotoxicity by PROTOX showed that compounds are not toxic (LD50 1000-2000 mg/kg). CONCLUSION Thirteen compounds, from which six are new ones, were synthesized, and twelve compounds were tested for antimicrobial activity. The studied compounds appeared to be promising potent and non-toxic antimicrobials, which could be considered as leads for new pharmaceutical agents.
T2  - Current Topics in Medicinal Chemistry
T1  - New Caffeic Acid Derivatives as Antimicrobial Agents: Design, Synthesis, Evaluation and Docking.
IS  - 4
VL  - 19
DO  - 10.2174/1568026619666190122152957
SP  - 292
EP  - 304
ER  - 

@article{
author = "Merlani, Maia and Barbakadze, Vakhtang and Amiranashvili, Lela and Gogilashvili, Lali and Poroikov, Vladimir and Petrou, Anthi and Geronikaki, Athina and Ćirić, Ana and Glamočlija, Jasmina and Soković, Marina",
year = "2019",
abstract = "BACKGROUND Phenolic acids (caffeic-, ferulic and p-coumaric acid) are widely distributed in the plant kingdom and exhibit broad spectrum of biological activities, including antimicrobial activity. OBJECTIVE The goal of this paper is the synthesis of some caffeic acid derivatives selected based on computer-aided predictions and evaluate their in vitro antimicrobial properties against Gram positive and Gram negative bacteria and also a series of fungi. METHODS In silico prediction of biological activity was used to identify the most promising structures for synthesis and biological testing, and the putative mechanisms of their antimicrobial action. The designed compounds were synthesized using classical organic synthesis methods. The antimicrobial activity was studied using microdilution method. RESULTS Twelve tested compounds have shown good antibacterial activity. Five out of twelve tested compounds appeared to be more active than the reference drugs ampicillin and streptomycin. Despite that all compounds exhibited good activity against all bacteria tested, the sensitivity of bacteria towards compounds in general was different. The evaluation of antifungal activity revealed that all compounds were more active than ketoconazole, while seven compounds (2, 3, 4, 5, 7, 8 and 12) appeared to be more active than bifonazole. Docking results indicate that gyrase inhibition is the putative mechanism of antibacterial action while the inhibition of 14α-demethylase may be responsible for antifungal action. Prediction of cytotoxicity by PROTOX showed that compounds are not toxic (LD50 1000-2000 mg/kg). CONCLUSION Thirteen compounds, from which six are new ones, were synthesized, and twelve compounds were tested for antimicrobial activity. The studied compounds appeared to be promising potent and non-toxic antimicrobials, which could be considered as leads for new pharmaceutical agents.",
journal = "Current Topics in Medicinal Chemistry",
title = "New Caffeic Acid Derivatives as Antimicrobial Agents: Design, Synthesis, Evaluation and Docking.",
number = "4",
volume = "19",
doi = "10.2174/1568026619666190122152957",
pages = "292-304"
}

Merlani, M., Barbakadze, V., Amiranashvili, L., Gogilashvili, L., Poroikov, V., Petrou, A., Geronikaki, A., Ćirić, A., Glamočlija, J.,& Soković, M.. (2019). New Caffeic Acid Derivatives as Antimicrobial Agents: Design, Synthesis, Evaluation and Docking.. in Current Topics in Medicinal Chemistry, 19(4), 292-304.
https://doi.org/10.2174/1568026619666190122152957

Merlani M, Barbakadze V, Amiranashvili L, Gogilashvili L, Poroikov V, Petrou A, Geronikaki A, Ćirić A, Glamočlija J, Soković M. New Caffeic Acid Derivatives as Antimicrobial Agents: Design, Synthesis, Evaluation and Docking.. in Current Topics in Medicinal Chemistry. 2019;19(4):292-304.
doi:10.2174/1568026619666190122152957 .

Merlani, Maia, Barbakadze, Vakhtang, Amiranashvili, Lela, Gogilashvili, Lali, Poroikov, Vladimir, Petrou, Anthi, Geronikaki, Athina, Ćirić, Ana, Glamočlija, Jasmina, Soković, Marina, "New Caffeic Acid Derivatives as Antimicrobial Agents: Design, Synthesis, Evaluation and Docking." in Current Topics in Medicinal Chemistry, 19, no. 4 (2019):292-304,
https://doi.org/10.2174/1568026619666190122152957 . .

TY  - JOUR
AU  - Merlani, Maia
AU  - Barbakadze, Vakhtang
AU  - Amiranashvili, Lela
AU  - Gogilashvili, Lali
AU  - Poroikov, Vladimir
AU  - Petrou, Anthi
AU  - Geronikaki, Athina
AU  - Ćirić, Ana
AU  - Glamočlija, Jasmina
AU  - Soković, Marina
PY  - 2019
UR  - http://www.eurekaselect.com/169251/article
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3346
AB  - BACKGROUND Phenolic acids (caffeic-, ferulic and p-coumaric acid) are widely distributed in the plant kingdom and exhibit broad spectrum of biological activities, including antimicrobial activity. OBJECTIVE The goal of this paper is the synthesis of some caffeic acid derivatives selected based on computer-aided predictions and evaluate their in vitro antimicrobial properties against Gram positive and Gram negative bacteria and also a series of fungi. METHODS In silico prediction of biological activity was used to identify the most promising structures for synthesis and biological testing, and the putative mechanisms of their antimicrobial action. The designed compounds were synthesized using classical organic synthesis methods. The antimicrobial activity was studied using microdilution method. RESULTS Twelve tested compounds have shown good antibacterial activity. Five out of twelve tested compounds appeared to be more active than the reference drugs ampicillin and streptomycin. Despite that all compounds exhibited good activity against all bacteria tested, the sensitivity of bacteria towards compounds in general was different. The evaluation of antifungal activity revealed that all compounds were more active than ketoconazole, while seven compounds (2, 3, 4, 5, 7, 8 and 12) appeared to be more active than bifonazole. Docking results indicate that gyrase inhibition is the putative mechanism of antibacterial action while the inhibition of 14α-demethylase may be responsible for antifungal action. Prediction of cytotoxicity by PROTOX showed that compounds are not toxic (LD50 1000-2000 mg/kg). CONCLUSION Thirteen compounds, from which six are new ones, were synthesized, and twelve compounds were tested for antimicrobial activity. The studied compounds appeared to be promising potent and non-toxic antimicrobials, which could be considered as leads for new pharmaceutical agents.
T2  - Current Topics in Medicinal Chemistry
T1  - New Caffeic Acid Derivatives as Antimicrobial Agents: Design, Synthesis, Evaluation and Docking.
IS  - 4
VL  - 19
DO  - 10.2174/1568026619666190122152957
SP  - 292
EP  - 304
ER  - 

@article{
author = "Merlani, Maia and Barbakadze, Vakhtang and Amiranashvili, Lela and Gogilashvili, Lali and Poroikov, Vladimir and Petrou, Anthi and Geronikaki, Athina and Ćirić, Ana and Glamočlija, Jasmina and Soković, Marina",
year = "2019",
abstract = "BACKGROUND Phenolic acids (caffeic-, ferulic and p-coumaric acid) are widely distributed in the plant kingdom and exhibit broad spectrum of biological activities, including antimicrobial activity. OBJECTIVE The goal of this paper is the synthesis of some caffeic acid derivatives selected based on computer-aided predictions and evaluate their in vitro antimicrobial properties against Gram positive and Gram negative bacteria and also a series of fungi. METHODS In silico prediction of biological activity was used to identify the most promising structures for synthesis and biological testing, and the putative mechanisms of their antimicrobial action. The designed compounds were synthesized using classical organic synthesis methods. The antimicrobial activity was studied using microdilution method. RESULTS Twelve tested compounds have shown good antibacterial activity. Five out of twelve tested compounds appeared to be more active than the reference drugs ampicillin and streptomycin. Despite that all compounds exhibited good activity against all bacteria tested, the sensitivity of bacteria towards compounds in general was different. The evaluation of antifungal activity revealed that all compounds were more active than ketoconazole, while seven compounds (2, 3, 4, 5, 7, 8 and 12) appeared to be more active than bifonazole. Docking results indicate that gyrase inhibition is the putative mechanism of antibacterial action while the inhibition of 14α-demethylase may be responsible for antifungal action. Prediction of cytotoxicity by PROTOX showed that compounds are not toxic (LD50 1000-2000 mg/kg). CONCLUSION Thirteen compounds, from which six are new ones, were synthesized, and twelve compounds were tested for antimicrobial activity. The studied compounds appeared to be promising potent and non-toxic antimicrobials, which could be considered as leads for new pharmaceutical agents.",
journal = "Current Topics in Medicinal Chemistry",
title = "New Caffeic Acid Derivatives as Antimicrobial Agents: Design, Synthesis, Evaluation and Docking.",
number = "4",
volume = "19",
doi = "10.2174/1568026619666190122152957",
pages = "292-304"
}

Merlani, M., Barbakadze, V., Amiranashvili, L., Gogilashvili, L., Poroikov, V., Petrou, A., Geronikaki, A., Ćirić, A., Glamočlija, J.,& Soković, M.. (2019). New Caffeic Acid Derivatives as Antimicrobial Agents: Design, Synthesis, Evaluation and Docking.. in Current Topics in Medicinal Chemistry, 19(4), 292-304.
https://doi.org/10.2174/1568026619666190122152957

Merlani M, Barbakadze V, Amiranashvili L, Gogilashvili L, Poroikov V, Petrou A, Geronikaki A, Ćirić A, Glamočlija J, Soković M. New Caffeic Acid Derivatives as Antimicrobial Agents: Design, Synthesis, Evaluation and Docking.. in Current Topics in Medicinal Chemistry. 2019;19(4):292-304.
doi:10.2174/1568026619666190122152957 .

Merlani, Maia, Barbakadze, Vakhtang, Amiranashvili, Lela, Gogilashvili, Lali, Poroikov, Vladimir, Petrou, Anthi, Geronikaki, Athina, Ćirić, Ana, Glamočlija, Jasmina, Soković, Marina, "New Caffeic Acid Derivatives as Antimicrobial Agents: Design, Synthesis, Evaluation and Docking." in Current Topics in Medicinal Chemistry, 19, no. 4 (2019):292-304,
https://doi.org/10.2174/1568026619666190122152957 . .

TY  - JOUR
AU  - Nadaraia, Nanuli Sh.
AU  - Amiranashvili, Lela Sh.
AU  - Merlani, Maia
AU  - Kakhabrishvili, Meri L.
AU  - Barbakadze, Nana N.
AU  - Geronikaki, Athina
AU  - Petrou, Anthi
AU  - Poroikov, Vladimir
AU  - Ćirić, Ana
AU  - Glamočlija, Jasmina
AU  - Soković, Marina
PY  - 2019
UR  - https://www.sciencedirect.com/science/article/pii/S0039128X19300376?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3274
AB  - Fourteen steroid compounds were in silico evaluated using computer program PASS as antimicrobial agents. The experimental studies evaluation revealed that all compounds have good antibacterial activity with MIC at range of 0.003-0.96 mg/mL and MBC 0.06-1.92 mg/mL. Almost all compounds except of compound 4 (3β-acetoxy-1/-p-chlorophenyl-3/-methyl-5α-androstano[17,16-d]pyrazoline) were more potent than Ampicillin, and they were equipotent or more potent than Streptomycine. All compounds exhibited good antifungal activity with MIC at 0.003-0.96 mg/mL and MFC at 0.006-1.92 mg/mL but with different sensitivity against fungi tested. According to docking studies 14-alpha demethylase inhibition may be responsible for antifungal activity. Prediction of toxicity by PROTOX and GUSAR revealed that compounds have low toxicity and can be considered as potential lead compounds for the further studies.
T2  - Steroids
T1  - Novel antimicrobial agents' discovery among the steroid derivatives.
VL  - 144
DO  - 10.1016/j.steroids.2019.02.012
SP  - 52
EP  - 65
ER  - 

@article{
author = "Nadaraia, Nanuli Sh. and Amiranashvili, Lela Sh. and Merlani, Maia and Kakhabrishvili, Meri L. and Barbakadze, Nana N. and Geronikaki, Athina and Petrou, Anthi and Poroikov, Vladimir and Ćirić, Ana and Glamočlija, Jasmina and Soković, Marina",
year = "2019",
abstract = "Fourteen steroid compounds were in silico evaluated using computer program PASS as antimicrobial agents. The experimental studies evaluation revealed that all compounds have good antibacterial activity with MIC at range of 0.003-0.96 mg/mL and MBC 0.06-1.92 mg/mL. Almost all compounds except of compound 4 (3β-acetoxy-1/-p-chlorophenyl-3/-methyl-5α-androstano[17,16-d]pyrazoline) were more potent than Ampicillin, and they were equipotent or more potent than Streptomycine. All compounds exhibited good antifungal activity with MIC at 0.003-0.96 mg/mL and MFC at 0.006-1.92 mg/mL but with different sensitivity against fungi tested. According to docking studies 14-alpha demethylase inhibition may be responsible for antifungal activity. Prediction of toxicity by PROTOX and GUSAR revealed that compounds have low toxicity and can be considered as potential lead compounds for the further studies.",
journal = "Steroids",
title = "Novel antimicrobial agents' discovery among the steroid derivatives.",
volume = "144",
doi = "10.1016/j.steroids.2019.02.012",
pages = "52-65"
}

Nadaraia, N. Sh., Amiranashvili, L. Sh., Merlani, M., Kakhabrishvili, M. L., Barbakadze, N. N., Geronikaki, A., Petrou, A., Poroikov, V., Ćirić, A., Glamočlija, J.,& Soković, M.. (2019). Novel antimicrobial agents' discovery among the steroid derivatives.. in Steroids, 144, 52-65.
https://doi.org/10.1016/j.steroids.2019.02.012

Nadaraia NS, Amiranashvili LS, Merlani M, Kakhabrishvili ML, Barbakadze NN, Geronikaki A, Petrou A, Poroikov V, Ćirić A, Glamočlija J, Soković M. Novel antimicrobial agents' discovery among the steroid derivatives.. in Steroids. 2019;144:52-65.
doi:10.1016/j.steroids.2019.02.012 .

Nadaraia, Nanuli Sh., Amiranashvili, Lela Sh., Merlani, Maia, Kakhabrishvili, Meri L., Barbakadze, Nana N., Geronikaki, Athina, Petrou, Anthi, Poroikov, Vladimir, Ćirić, Ana, Glamočlija, Jasmina, Soković, Marina, "Novel antimicrobial agents' discovery among the steroid derivatives." in Steroids, 144 (2019):52-65,
https://doi.org/10.1016/j.steroids.2019.02.012 . .