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

Trawally M., Demir-Yazici K., DİNGİŞ BİRGÜL S. İ., Kaya K., AKDEMİR A., Guezl-Akdemir O.

BIOORGANIC CHEMISTRY, cilt.121, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 121
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1016/j.bioorg.2022.105688
  • Dergi Adı: BIOORGANIC CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: 4-Thiazolidinone, Spirothiazolidinone, Mandelic acid, Mycobacterium tuberculosis, Molecular docking, Molecular dynamics, Enoyl-[acyl-carrier-protein]-reductase, Mt InhA, MYCOBACTERIUM-TUBERCULOSIS, ANTIMICROBIAL ACTIVITY, BIOLOGICAL EVALUATION, ANTITUBERCULOSIS ACTIVITY, SALICYLATE SYNTHASE, CRYSTAL-STRUCTURES, DERIVATIVES, INHIBITION, 4-THIAZOLIDINONE, POTENT
  • İstanbul Teknik Üniversitesi Adresli: Evet

Özet

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 mu g/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.