Molecular modeling and in vitro antiproliferative activity studies of some imidazole and isoxazole derivatives

Five compounds were synthesized and tested as in vitro against two different cancer cell lines to find out their antiproliferative activities. The results showed that a compound including imidazole core, 2b, had the highest cytotoxic activity in both cell lines for both 24 h and 48 h incubation times. The bind-ing potential of the relatively active derivative, 2b, with topoisomerase I was assessed through molecular docking. The stability of the complexes from the docking process was investigated through molecular dynamics (MD) simulations. Computational pharmacokinetics analysis was also performed. The computa-tional analysis in this study revealed that 2b could bind to topoisomerase I but less than the reference drug. The in silico pharmacokinetics also exhibited that the synthesized compounds had drug-like prop-erties.(c) 2023 Published by Elsevier B.V.

Automated summary

Five compounds were synthesized and tested for their antiproliferative activities against two cancer cell lines. Compound 2b, which contains an imidazole core, showed the highest cytotoxic activity in both cell lines after 24 and 48 hours of incubation. The binding potential of 2b with topoisomerase I was assessed through molecular docking and the stability of the complexes was investigated through molecular dynamics simulations. Computational pharmacokinetics analysis revealed that 2b could bind to topoisomerase I, but to a lesser extent than the reference drug. In silico pharmacokinetics also showed that the synthesized compounds had drug-like properties.