Evaluation of new 2-hydroxy-N-(4-oxo-2-substituted phenyl-1,3- thiazolidin-3-yl)-2-phenylacetamide derivatives as potential antimycobacterial agents

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Guzel-Akdemir O., DEMİR YAZICI K., Trawally M., Dingis-Birgul S. İ., AKDEMİR A.

ORGANIC COMMUNICATIONS, vol.13, no.2, pp.33-50, 2020 (ESCI) identifier identifier

  • Publication Type: Article / Article
  • Volume: 13 Issue: 2
  • Publication Date: 2020
  • Doi Number: 10.25135/acg.oc.78.20.05.1655
  • Journal Name: ORGANIC COMMUNICATIONS
  • Journal Indexes: Emerging Sources Citation Index (ESCI), Scopus, Academic Search Premier, Directory of Open Access Journals, TR DİZİN (ULAKBİM)
  • Page Numbers: pp.33-50
  • Keywords: Mycobacterium tuberculosis, 2-hydroxy-2-phenylacetohydrazide, mercaptoethanoic acid, 2-mercaptopropanoic acid, 4-oxo-1,3-thiazolidines, molecular modelling, MYCOBACTERIUM-TUBERCULOSIS, CRYSTAL-STRUCTURE, INHIBITORS, TARGET, 4-THIAZOLIDINONE
  • Bezmialem Vakıf University Affiliated: Yes

Abstract

A small collection of 2-hydroxy-N-(5-methyl/nonsubstituted 4-oxo-2-substituted phenyl-1,3-thiazolidin-3-yl)-2-phenylacetamides (3-16) was synthesized from the cyclocondensation of 2-hydroxy-2-phenyl-N'-[(substitutedphenyl)methylene]acetohydrazides (2) and mercaptoethanoic acid or 2-mercaptopropanoic acid, characterized with spectral and elemental analysis. In order to explore their antimycobacterial potential, newly synthesized fourteen compounds were screened for their inhibitory activity against Mycobacterium tuberculosis strain H37Rv at 6.25 mu g/mL with in-vitro primary tests. Compound 7 was found to provide the highest inhibition (98%) M. tuberculosis strain H37Rv, while most of the new derivatives showed different inhibition ratios. For the search of the putative targets which are considered as related to the antimycobacterial activity of these molecules, docking studies were performed. With molecular dynamic simulations, further possible interactions between ligands and the active site of the selected enzymes were investigated. Eventually, molecular modelling studies indicated that at least part of the mechanism of action of these compounds may be mediated by inhibition of MtInhA.