5-(1 H-Indol-3-ylmethylene)-4-oxo-2-thioxothiazolidin-3-yl)alkancarboxylic Acids as Antimicrobial Agents: Synthesis, Biological Evaluation, and Molecular Docking Studies

Volodymyr Horishny; Victor Kartsev; Athina Geronikaki; Vasyl Matiychuk; Anthi Petrou; Jasmina Glamoclija; Ana Ciric; Marina Sokovic

doi:10.3390/molecules25081964

5-(1 H-Indol-3-ylmethylene)-4-oxo-2-thioxothiazolidin-3-yl)alkancarboxylic Acids as Antimicrobial Agents: Synthesis, Biological Evaluation, and Molecular Docking Studies

Molecules. 2020 Apr 23;25(8):1964. doi: 10.3390/molecules25081964.

Authors

Volodymyr Horishny¹, Victor Kartsev², Athina Geronikaki³, Vasyl Matiychuk⁴, Anthi Petrou³, Jasmina Glamoclija⁵, Ana Ciric⁵, Marina Sokovic⁵

Affiliations

¹ Department of Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, 79010 Lviv, Ukraine.
² InterBioScreen, 85355 Moscow, Russia.
³ Department of Phram Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
⁴ Department of Chemistry, Ivan Franko National University of Lviv, Kyryla i Mefodia 6, 79005 Lviv, Ukraine.
⁵ Mycological Laboratory, Institute of Biological Research Sinisa Stankovic, National Institute of Republic of Serbia, Belgrade University, 11000 Belgrade, Serbia.

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.

Keywords: CYP51; Candida albicans 14α-demethylase; E. coli MurB; antifungal; antimicrobial; indole; molecular docking.

MeSH terms

Anti-Infective Agents / chemical synthesis
Anti-Infective Agents / chemistry*
Anti-Infective Agents / pharmacology*
Chemistry Techniques, Synthetic
Heterocyclic Compounds / chemical synthesis
Heterocyclic Compounds / chemistry*
Heterocyclic Compounds / pharmacology*
Molecular Conformation
Molecular Docking Simulation
Molecular Dynamics Simulation
Molecular Structure
Structure-Activity Relationship

Substances

Anti-Infective Agents
Heterocyclic Compounds