Click chemistry-assisted synthesis of benzimidazole-1,2,3-triazole hybrids as potential anticancer and antioxidant agents: Integrated in vitro , in silico docking, ADMET, molecular dynamics, and DFT studies

This study details the rational design and synthesis of benzimidazole–1,2,3-triazole hybrids (10a-10o) as potential CDK2 inhibitors for anticancer treatment. Molecular docking showed strong binding within the ATP-binding site, with key hydrogen bonds to Leu83 and Asp86, as well as hydrophobic and π–π interactions. Docking scores ranged from −7.93 to −3.09 kcal/mol, and MM/GBSA binding energies reached up to −50.01 kcal/mol. Molecular dynamics simulations over 100 ns verified the stability of the protein–ligand complexes. In vitro tests against MCF-7 cells revealed that compound 10e (IC50 = 14.55 µM) was more effective than doxorubicin (IC50 = 15.77 µM), while 10c (IC50 = 20.47 µM) also showed significant activity. Antioxidant assays indicated that compound 10c (IC50 = 50.80 µg/mL) had radical scavenging activity comparable to ascorbic acid (IC50 = 45.20 µg/mL). DFT analysis found that 10e has the lowest HOMO–LUMO gap, implying higher reactivity. PCA and ADMET assessments further supported its potential as a promising drug candidate.