2026/02/13 by Sara Jamal Meknas, E. Al-Shalabi, Rima Hajjo +7 · 1 voice
Biochemistry, Genetics and Molecular Biology · Chemistry · Health Professions · #Cancer therapeutics and mechanisms #Diverse Scientific Research Studies #Synthesis and biological activity
paper · pdf · doi:10.3390/molecules31040655
openalex publication_date 2026/02/13 · openalex created_date 2026/02/14 · openalex updated_date 2026/07/22
Cancer remains the second leading cause of death worldwide, highlighting the urgent need for novel therapeutic agents. In this work, twenty derivatives of N-benzyl-6-chloro-4-hydroxy-2-quinolone-3-carboxamides were synthesized and spectroscopically analyzed using FT-IR, NMR (1H and 13C), and elemental analysis. Substitution of benzyl moiety with o-CH3 (8), p-OCH3 (10), m-CH3 (18), p-CH3 (19), and p-CF3 (21) demonstrated three-fold distinct cytotoxicity against human colon cancer (HCT-116) cells with IC50s of 72.0, 100.0–112.0 µM. The cheminformatics calculations disclosed that the analogues possess diverse physicochemical properties and invariable predictions across six drug-likeness scoring models, supporting their potential cytotoxicity profile against colorectal cancer cell lines (Caco-2 and HCT-116). The docking studies against both wild-type and mutant PI3Kα clarified binding interactions, implying that particular functionalities improve efficacy and selectivity. This study provides further evidence for the therapeutic promise of quinolones in targeting cancer-specific pathways and expedites the process for developing potent anticancer agents.