Senthilkumar N, Sarveswari S, Choudhari Prafulla, Chaudhari Somdatta, Islam Imadul, Tamboli Yasinalli, Vijayakumar V
Department of Chemistry, Vellore Institute of Technology, Vellore, Tamil Nadu, 632 014, India.
Department of Pharmaceutical Chemistry, Bharati Vidyapeeth College of Pharmacy, Kolhapur, India.
BMC Chem. 2025 Jun 9;19(1):161. doi: 10.1186/s13065-025-01532-z.
A new set of benzimidazole-thiadiazole derivatives has been designed and synthesized using 2-(chloromethyl)-1H-benzo[d]imidazole (1). Compounds 4a-m were achieved by amide bond formation using acid chlorides and pyridine in 1, 2-dichloroethane. The newly synthesized compounds were characterized and subjected to cytotoxicity studies against HeLa cells. Compounds 4c, 4 d, and 4e exhibited good inhibitory activity with IC values of 15, 25, and 25 µM, respectively. Molecular docking studies were performed to elucidate the binding interactions of compounds 4c and 4e with human Casein kinase-2 (CK2). Compound 4c exhibited maximum cytotoxicity against HeLa cells with the lowest binding energy values of -8.61 kcal/mol towards CK2. Compound 4c underwent molecular dynamics (MD) simulations to assess their stability and interactions within the active site. Density functional theory (DFT) calculations also provided insights into the synthesised compounds' electronic structure, reactivity, and charge distribution.
使用2-(氯甲基)-1H-苯并[d]咪唑(1)设计并合成了一组新的苯并咪唑-噻二唑衍生物。化合物4a - m是通过在1,2-二氯乙烷中使用酰氯和吡啶形成酰胺键来制备的。对新合成的化合物进行了表征，并对其针对HeLa细胞的细胞毒性进行了研究。化合物4c、4d和4e表现出良好的抑制活性，IC值分别为15、25和25 μM。进行了分子对接研究，以阐明化合物4c和4e与人酪蛋白激酶-2(CK2)的结合相互作用。化合物4c对HeLa细胞表现出最大的细胞毒性，对CK2的最低结合能值为-8.61 kcal/mol。对化合物4c进行了分子动力学(MD)模拟，以评估其在活性位点内的稳定性和相互作用。密度泛函理论(DFT)计算也为合成化合物的电子结构、反应性和电荷分布提供了见解。
