2. Academic Validation
  3. Mandelic acid-based spirothiazolidinones targeting M. tuberculosis: Synthesis, in vitro and in silico investigations

Mandelic acid-based spirothiazolidinones targeting M. tuberculosis: Synthesis, in vitro and in silico investigations

  • Bioorg Chem. 2022 Apr;121:105688. doi: 10.1016/j.bioorg.2022.105688.
Muhammed Trawally 1,  Kübra Demir-Yazıcı 1,  Serap İpek Dingiş-Birgül 2,  Kerem Kaya 3,  Atilla Akdemir 2,  Özlen Güzel-Akdemir 4
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey.
  • 2 Computer-Aided Drug Discovery Laboratory, Department of Pharmacology, Faculty of Pharmacy, Bezmialem Vakif University, Istanbul, Turkey.
  • 3 Department of Chemistry, Istanbul Technical University, Istanbul, Turkey.
  • 4 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey. Electronic address: [email protected].
PMID: 35189443 DOI: 10.1016/j.bioorg.2022.105688
Abstract

A series of new spirothiazolidinone derivatives with a mandelic acid moiety were synthesized and subsequently tested in growth inhibition assays against Mycobacterium tuberculosis strain H37Rv. Compound 16 displayed the highest inhibition value of 98% at lower than 6.25 µg/mL concentration. A single crystal X-ray analysis was conducted on this compound to confirm the structure and determine its absolute configuration. Afterwards, reverse docking and molecular dynamics simulations of this specific stereoisomer were performed against a selection of 10 putative targets of M. tuberculosis to suggest possible mechanisms of action. Our results suggest HadAB, Pks13, DprE1, FadD32 and InhA as possible target proteins for the observed antimycobacterial activity of compound 16.

Keywords

4-Thiazolidinone; Enoyl-[acyl-carrier-protein]-reductase; Mandelic acid; Molecular docking; Molecular dynamics; MtInhA; Mycobacterium tuberculosis; Spirothiazolidinone.

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