Design, synthesis, biological assessment, and in-Silico studies of 1,2,4-triazolo[1,5-a]pyrimidine derivatives as tubulin polymerization inhibitors
- Bioorg Chem. 2022 Apr;121:105687. doi: 10.1016/j.bioorg.2022.105687.
- 1. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt. Electronic address: [email protected].
- 2. Medicinal Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt.
- 3. Medicinal Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt; Medicinal Chemistry Department, Faculty of Pharmacy, Sinai University-Kantra Branch, Egypt.
- 4. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt; Medicinal Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.
A series of 1,2,4-triazolo[1,5-a]pyrimidine derivatives have been designed and synthesized as combretastatin CA-4 analogs. They were screened for Anticancer and tubulin polymerization inhibition activities. The trimethoxyphenyl 1,2,4-triazolo[1,5-a]pyrimidine derivative 4c showed significant antiproliferative activity in which it exhibited IC50 = 0.53 μM against HCT-116 Cancer cell line. It was further tested as a tubulin polymerization inhibitor showing an IC50 = 3.84 μM if compared to combretastatin IC50 = 1.10 μM. Further mechanism studies revealed that compound 4c could obviously inhibit the proliferation of HCT-116 Cancer cells by inducing Apoptosis and arresting the cell cycle at the G2/M phase. Furthermore, docking studies showed that compound 4c illustrated good fitting to the colchicine binding site of tubulin. Thus, it is considered an Anticancer lead compound worthy of further development as a tubulin polymerization inhibitor.
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Cat. No.Product NameDescriptionTargetResearch Area
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Research Areas: Cancer