Synthesis and Biochemical Evaluation of Novel Coumarin Derivatives as Anticancer and Anti-HIV Inhibitors Targeting CDK2

Abstract

The present investigation dealt with finding new compounds that can act on both cancer and HIV-1 reverse transcriptase targeting CDK2. We constructed a library of new coumarin derivatives and developed a fingerprint pharmacophore model by using known CDK2 inhibitors (in clinical trial phase) and HIV-1 reverse transcriptase crystal structure (3DLG). The proposed library was mapped to the generated pharmacophore models and according to their fit-values; they were selected for docking into CDK2 enzyme. Compounds with high binding energy were selected for chemical preparation. Developing or adapting methods for the preparation of the selected compounds was applied and structures of the target compounds have been established by spectral analysis data. Five compounds 7b, 9d, 7c, 7d and 8c have shown very good anti-HIV activity in MT-4 cells. Similarly, five compounds 7b, 9d, 8b, 7c and 7d have exhibited very significant CDK2 inhibition activity. Compounds 7b and 7d were found to have dual anti-HIV and anticancer activities.