2. Academic Validation
  3. Design and Synthesis of Thiadiazole Derivatives as Dual EGFR/COX‑2 Inhibitors with Anticancer and Anti-inflammatory Activities

Design and Synthesis of Thiadiazole Derivatives as Dual EGFR/COX‑2 Inhibitors with Anticancer and Anti-inflammatory Activities

  • ACS Omega. 2025 Dec 12;10(51):63276-63292. doi: 10.1021/acsomega.5c09752.
Arzu Hidir 1 2,  Derya Osmaniye 1 3,  Begüm Nurpelin Sağlik Özkan 1 3,  Serkan Levent 3 4,  Zafer Asım Kaplancikli 1 5,  Yusuf Özkay 1 3
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey.
  • 2 Institute of Graduate Education, Anadolu University, Eskişehir 26470, Turkey.
  • 3 Central Research Laboratory, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey.
  • 4 Department of Analytical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir 26470, Turkey.
  • 5 Department of Pharmacy Services, Vocational School of Health Services, Bilecik Seyh Edebali University, Bilecik 11230,Turkey.
PMID: 41487259 DOI: 10.1021/acsomega.5c09752
Abstract

In this study, 20 new compounds with thiadiazole structures were synthesized based on Alpelisib. The benzene ring, a bioisostere of the pyridine ring in the lead compound, was used in the synthesized compounds, and derivatives containing different substituents were used to observe modifications that could affect activity. Furthermore, because combined therapies are known to be more effective in Cancer therapy, attempts were made to design compounds capable of dual inhibition of EGFR-COX-2 by adding sulfonamide substitutions to some compounds. The structures of the compounds were confirmed by IR, 1H NMR, 13C NMR, and HRMS spectral analyses. A549 and MCF-7 cell lines were used to measure Anticancer activity, and in vitro assays were conducted. For compounds 3j and 3o, further activity studies, molecular docking, and molecular dynamics studies were performed. The compounds' EGFR and COX-2 inhibitory potential was investigated.

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