TiO 2 ‐Catalyzed One‐Pot Synthesis, Molecular Docking, and Anticancer Activity of Novel Quinoline‐Pyrazole Hybrid Derivative

ABSTRACT A series of novel quinoline‐pyrazole hybrid derivatives (4a–j) were synthesized via a rapid, eco‐friendly one‐pot three‐component condensation using TiO 2 nanoparticles as catalysts. The reaction proceeded efficiently at room temperature in methanol, yielding products within 5–10 min. All compounds were evaluated for cytotoxicity against MCF‐7 and HepG2 cancer cell lines using the MTT assay. Compound 4e (4‐OCH₃) exhibited the most potent activity, with IC 50 values of 9.1 ± 0.5 μM (MCF‐7) and 24.2 ± 0.7 μM (HepG2), comparable to doxorubicin (10.6 ± 0.2 μM for MCF‐7). Structure–activity relationship analysis revealed that electron‐donating groups (4‐OCH 3 , 3‐OCH 3 , and 4‐CH 3 ). Molecular docking studies against EGFR (1 M17) and VEGFR2 (3VHE) showed that 4e exhibited superior binding affinity (−6.34 and −7.51 kcal/mol) compared with erlotinib and sorafenib, with key hydrogen bonds and hydrophobic interactions in the ATP‐binding sites. These findings establish quinoline‐pyrazole hybrids as promising dual EGFR/VEGFR2 inhibitors, with compound 4e being a lead candidate for anticancer drug development.