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  - Horishny, Volodymyr
AU  - Kartsev, Victor
AU  - Geronikaki, Athina
AU  - Matiychuk, Vasyl
AU  - Petrou, Anthi
AU  - Glamočlija, Jasmina
AU  - Ćirić, Ana
AU  - Soković, Marina
PY  - 2020
UR  - https://www.mdpi.com/1420-3049/25/8/1964
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3661
AB  - Background: Infectious diseases symbolize a global consequential strain on public health security and impact on the socio-economic stability all over the world. The increasing resistance to the current antimicrobial treatment has resulted in crucial need for the discovery and development of novel entity for the infectious treatment with different modes of action that could target both sensitive and resistant strains. Methods: Compounds were synthesized using classical methods of organic synthesis. Results: All 20 synthesized compounds showed antibacterial activity against eight Gram-positive and Gram-negative bacterial species. It should be mentioned that all compounds exhibited better antibacterial potency than ampicillin against all bacteria tested. Furthermore, 18 compounds appeared to be more potent than streptomycin against Staphylococcus aureus, Enterobacter cloacae, Pseudomonas aeruginosa, Listeria monocytogenes, and Escherichia coli. Three the most active compounds 4h, 5b, and 5g appeared to be more potent against MRSA than ampicillin, while streptomycin did not show any bactericidal activity. All three compounds displayed better activity also against resistant strains P. aeruginosa and E. coli than ampicillin. Furthermore, all compounds were able to inhibit biofilm formation 2- to 4-times more than both reference drugs. Compounds were evaluated also for their antifungal activity against eight species. The evaluation revealed that all compounds exhibited antifungal activity better than the reference drugs bifonazole and ketoconazole. Molecular docking studies on antibacterial and antifungal targets were performed in order to elucidate the mechanism of antibacterial activity of synthesized compounds. Conclusion: All tested compounds showed good antibacterial and antifungal activity better than that of reference drugs and three the most active compounds could consider as lead compounds for the development of new more potent agents.
PB  - MDPI AG
T2  - Molecules
T1  - 5-(1H-Indol-3-ylmethylene)-4-oxo-2-thioxothiazolidin-3-yl)alkancarboxylic Acids as Antimicrobial Agents: Synthesis, Biological Evaluation, and Molecular Docking Studies
IS  - 8
VL  - 25
DO  - 10.3390/molecules25081964
SP  - 1964
ER  - 

@article{
author = "Horishny, Volodymyr and Kartsev, Victor and Geronikaki, Athina and Matiychuk, Vasyl and Petrou, Anthi and Glamočlija, Jasmina and Ćirić, Ana and Soković, Marina",
year = "2020",
abstract = "Background: Infectious diseases symbolize a global consequential strain on public health security and impact on the socio-economic stability all over the world. The increasing resistance to the current antimicrobial treatment has resulted in crucial need for the discovery and development of novel entity for the infectious treatment with different modes of action that could target both sensitive and resistant strains. Methods: Compounds were synthesized using classical methods of organic synthesis. Results: All 20 synthesized compounds showed antibacterial activity against eight Gram-positive and Gram-negative bacterial species. It should be mentioned that all compounds exhibited better antibacterial potency than ampicillin against all bacteria tested. Furthermore, 18 compounds appeared to be more potent than streptomycin against Staphylococcus aureus, Enterobacter cloacae, Pseudomonas aeruginosa, Listeria monocytogenes, and Escherichia coli. Three the most active compounds 4h, 5b, and 5g appeared to be more potent against MRSA than ampicillin, while streptomycin did not show any bactericidal activity. All three compounds displayed better activity also against resistant strains P. aeruginosa and E. coli than ampicillin. Furthermore, all compounds were able to inhibit biofilm formation 2- to 4-times more than both reference drugs. Compounds were evaluated also for their antifungal activity against eight species. The evaluation revealed that all compounds exhibited antifungal activity better than the reference drugs bifonazole and ketoconazole. Molecular docking studies on antibacterial and antifungal targets were performed in order to elucidate the mechanism of antibacterial activity of synthesized compounds. Conclusion: All tested compounds showed good antibacterial and antifungal activity better than that of reference drugs and three the most active compounds could consider as lead compounds for the development of new more potent agents.",
publisher = "MDPI AG",
journal = "Molecules",
title = "5-(1H-Indol-3-ylmethylene)-4-oxo-2-thioxothiazolidin-3-yl)alkancarboxylic Acids as Antimicrobial Agents: Synthesis, Biological Evaluation, and Molecular Docking Studies",
number = "8",
volume = "25",
doi = "10.3390/molecules25081964",
pages = "1964"
}

Horishny, V., Kartsev, V., Geronikaki, A., Matiychuk, V., Petrou, A., Glamočlija, J., Ćirić, A.,& Soković, M.. (2020). 5-(1H-Indol-3-ylmethylene)-4-oxo-2-thioxothiazolidin-3-yl)alkancarboxylic Acids as Antimicrobial Agents: Synthesis, Biological Evaluation, and Molecular Docking Studies. in Molecules
MDPI AG., 25(8), 1964.
https://doi.org/10.3390/molecules25081964

Horishny V, Kartsev V, Geronikaki A, Matiychuk V, Petrou A, Glamočlija J, Ćirić A, Soković M. 5-(1H-Indol-3-ylmethylene)-4-oxo-2-thioxothiazolidin-3-yl)alkancarboxylic Acids as Antimicrobial Agents: Synthesis, Biological Evaluation, and Molecular Docking Studies. in Molecules. 2020;25(8):1964.
doi:10.3390/molecules25081964 .

Horishny, Volodymyr, Kartsev, Victor, Geronikaki, Athina, Matiychuk, Vasyl, Petrou, Anthi, Glamočlija, Jasmina, Ćirić, Ana, Soković, Marina, "5-(1H-Indol-3-ylmethylene)-4-oxo-2-thioxothiazolidin-3-yl)alkancarboxylic Acids as Antimicrobial Agents: Synthesis, Biological Evaluation, and Molecular Docking Studies" in Molecules, 25, no. 8 (2020):1964,
https://doi.org/10.3390/molecules25081964 . .