Green Synthesis of Tetrahydrodipyrazolopyridines: In Silico and In Vitro Evaluation Against HepG2 Liver Cancer Cells

Tetrahydrodipyrazolopyridines (THDPPs), which play an important role in green synthesis, are obtained through environmentally friendly synthesis methods and are attracting increasing attention due to their remarkable biological and pharmacological activities. The aim of this study is to (i) obtain THDPPs using the green synthesis method, (ii) investigate molecular docking and molecular dynamic analysis of THDPPs, and (iii) evaluate their cytotoxic effects on HepG2 liver cancer cells. Structures of the synthesized THDPPs were elucidated using spectroscopic methods. The anticancer potential of THDPPs was evaluated using the MTT assay in the HepG2 liver cancer cell line, and some THDPPs were found to exhibit significant cytotoxic effects. Molecular docking analyses revealed that THDPPs had binding energies between −7.7 and −9.2 kcal/mol, higher than the standard drug 5‐fluorouracil (5‐Fu) having −5.5 kcal/mol. Furthermore, molecular dynamics simulation results were consistent with experimental findings, demonstrating that the compounds interact specifically with CDK8 (cyclin‐dependent kinase 8) protein. These findings suggested that the synthesized THDPPs may be promising candidates for anticancer agent development.