Novel thiadiazol derivatives; design, synthesis, biological activity, molecular docking and molecular dynamics

OSMANİYE D., EVREN A. E., Karaca Ş., ÖZKAY Y., KAPLANCIKLI Z. A.

Journal of Molecular Structure, vol.1272, 2023 (SCI-Expanded) identifier

  • Publication Type: Article / Article
  • Volume: 1272
  • Publication Date: 2023
  • Doi Number: 10.1016/j.molstruc.2022.134171
  • Journal Name: Journal of Molecular Structure
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, INSPEC
  • Keywords: Molecular docking, Molecular dynamics, Selective COX-2 inhibition, Thiadiazol
  • Bilecik Şeyh Edebali University Affiliated: Yes

Abstract

© 2022 Elsevier B.V.Currently, selective COX-2 inhibitors are used as a novel alternative approach in the course of pain management due to their reduced adverse that generally occur after COX-1 inhibition by non-selective COX inhibitors. In this work, 16 new thiadiazole derivatives (3a-3p) were designed, synthesized and biologically evaluated for their COX-1 and COX-2 inhibitory potential using the in vitro fluorometric method. The biological evaluation showed that compounds 3c and 3d displayed significant activity against COX-2 with IC50 values of 0.350±0.015 µM and 0.134±0.004 µM, respectively, making the compound 3d similar in its activity to the reference drug celecoxib (IC50=0.132±0.005 µM). Further docking simulation also revealed that the most active derivative (3d) interacted with the enzyme active site in a similar manner to celecoxib. The binding modes of the compound on COX-2 were fully elucidated by molecular dynamics studies.