3-Amino-5-(indol-3-yl)methylene-4-oxo-2-thioxothiazolidine Derivatives as Antimicrobial Agents: Synthesis, Computational and Biological Evaluation
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 sili...
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MDPI AG,
2020-09-01T00:00:00Z.
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| Ամփոփում: | 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 <i>S. aureus</i> (American Type Culture Collection ATCC 6538), while <i>L. monocytogenes</i> (NCTC 7973) was the most resistant. The best antibacterial activity was observed for compound <b>5d</b> (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 <b>5d, 5g,</b> and <b>5k</b> being evaluated against three resistant strains, Methicillin resistant <i>Staphilococcus aureus</i> (MRSA), <i>P. aeruginosa,</i> and <i>E. coli</i>, 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 <b>5d</b> was also more active than ampicillin towards resistant <i>P. aeruginosa</i> 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 <b>5g</b>. The most sensitive fungal was <i>T. viride</i> (IAM 5061), while <i>A. fumigatus</i> (human isolate<i>)</i> 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 <b>5d</b>, <b>5g</b>, <b>5k</b>, <b>7c</b> using thiazolyl blue tetrazolium bromide MTT assay. The docking studies indicated a probable involvement of <i>E. coli</i> Mur B inhibition in the antibacterial action, while CYP51 inhibition is likely responsible for the antifungal activity of the tested compounds. |
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| Նյութի նկարագրություն: | 10.3390/ph13090229 1424-8247 |