Synthesis, biological evaluation, molecular docking and molecular dynamic simulation studies of new 1,3,4-thiadiazole and 1,2,4-triazole derivatives as enolase-1 inhibitors

Özçal F. K., Çevik Ö., Kozan B., Mali S. N., Chaudhari S. Y., TOK F.

Journal of Molecular Structure, cilt.1367, 2026 (SCI-Expanded, Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 1367
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1016/j.molstruc.2026.146141
  • Dergi Adı: Journal of Molecular Structure
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Chimica, Compendex, INSPEC
  • Anahtar Kelimeler: 1,2,4-triazole, 1,3,4-thiadiazole, Bladder cancer, Cancer, Enolase, Thiosemicarbazide
  • Marmara Üniversitesi Adresli: Evet

Özet

Cancer is one of the leading health problems worldwide. The development of new chemotherapeutic agents is necessary against bladder cancer due to its high mortality rates and limited treatment options. For this purpose, twelve 1,3,4-thiadiazole (4a-4l) and twelve 1,2,4-triazole (5a-5l) compounds with a picoline structure were synthesized. IR, NMR (1H, 13C, 2D) and elemental analysis data were used to verify the structures of the compounds. The cytotoxic activities of the compounds were tested on bladder cancer (UM-UC-3) cells and mouse fibroblast (L929) cells using the MTT assay. Compounds 4f, 4g, 4l, 5g, 5j, 5k, and 5l exhibited selective cytotoxic activities against UM-UC-3 cells with IC50 values ranging from 11.21±2.06 µM to 78.67±6.62 µM within the series. Apoptosis induction and TOS levels of compounds 4f, 4g, 4l, 5g, 5j, 5k, and 5l were investigated by comparing them to the reference compound 5-fluorouracil. The inhibition rates of the compounds against the enolase-1 (ENO1) enzyme were also evaluated. Furthermore, molecular docking and molecular dynamics studies were conducted on 4l, the most potent compound in the series, using the ENO1 enzyme.