Synthesis and biological evaluation of novel pyridone derivatives containing 1,3,4-thiadiazol as potential anticancer agents

  • Bioorg Med Chem Lett. 2026 Aug:137:130654. doi: 10.1016/j.bmcl.2026.130654.
Zhiqiang Long  1 ,  Yizheng Li  2 ,  Renzhi Liu  1 ,  Xingtian Tang  1 ,  Huilin Zhang  1 ,  Shimin Xie  1 ,  Wenlin Xie  3
Affiliations
  • 1. School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201, China.
  • 2. Department of Oncology, Xiangya Hospital, Central South University, Hunan, Key Laboratory of Molecular Radiation Oncology, Changsha 410008, China.
  • 3. School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201, China; Key Laboratory of Theoretical Organic Chemistry and Function Molecule of Ministry of Education, Hunan University of Science and Technology, Xiangtan 411201, China; Hunan Provincal Key Laboratory of Controllable Preparation and Functional Application of Fine Polymers, Xiangtan 411201, China. Electronic address: [email protected].
PMID: 41967614 DOI: 10.1016/j.bmcl.2026.130654
Abstract

A series of novel 5,6-disubstituted pyridone derivatives containing 1,3,4-thiadiazol (3a-3p) were synthesized starting from 2,3-dihydroxypyridine via oxidation-Michael additions, condensations and cyclizations. The Anticancer activity of the newly synthesized compounds were evaluated against Gastric Cancer (MGC-803), hepatocellular Cancer (HepG2) and Pulmonary Cancer (PC-9) cell lines using the MTT assay. Most compounds exhibited antiproliferative activity against various Cancer cells in vitro. Compared with the standard drug 5-fluorouracil, compounds 3a, 3 g and 3 h showed better activity against MGC-803, HepG2 and PC-9 cell lines, respectively. Compound 3 h demonstrated the most potent antitumor activity with IC50 values of 2.43 μM, 1.73 μM and 4.03 μM against MGC-803, HepG2 and PC-9 cell lines, respectively, which was 1.7-4.5 folds more potent than 5-Fluorouracil (IC50 = 10.92 μM 7.15 μM and 6.88 μM against MGC-803, HepG2 and PC-9 cell lines respectively). These findings suggest that compound 3 h shows promise as a lead compound for the development of novel small-molecule Anticancer agents.

Keywords
2,3-dihydroxypyridine pyridine-2,3-diones thiadiazol antitumor activity.
Products