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.

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.

In this work we present the results of a study of the X-ray structure of 2-[(2,4-dimethoxyphenyl)amino]-1,3-thiazolidin-4-one. Using the FTIR spectra in solid state and results of ab initio calculations we explain the issue of the tautomerism of this molecule. The compound is shown to exist as the 2-amino tautomer rather 2-imino tautomer. Here we consider eight possible tautomers. On the basis of the vibrational spectra we can eliminate five possible tautomers, as not existing in the solid state. As the most possible tautomeric form we have found keto 2-amino form.Electronic supplementary materialThe online version of this article (doi:10.1007/s00894-014-2366-6) contains supplementary material, which is available to authorized users.

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.

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