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  - 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 . .