N-Benzyl-6-Chloro-4-Hydroxy-2-Quinolone-3-Carboxamides: Synthesis, Computational Studies, and Biological Investigation as Anticancer Agents
Sara Jamal Meknas, Eveen Al-Shalabi, Rima Hajjo, Sanaa K. Bardaweel, Ghassan Abushaikha, Kamal Sweidan, Swapnaa Balaji, Amit K. Tiwari, Haizhen A. Zhong, Dima A. Sabbah
TL;DR
Researchers synthesized and tested new quinolone compounds that show potential as anticancer agents, particularly against colon cancer cells.
Contribution
The study introduces new N-benzyl-6-chloro-4-hydroxy-2-quinolone-3-carboxamide derivatives with demonstrated cytotoxicity against colon cancer cells.
Findings
Five derivatives showed distinct cytotoxicity against HCT-116 cells with IC50 values ranging from 72.0 to 112.0 µM.
Cheminformatics and docking studies revealed drug-like properties and binding interactions with PI3Kα, suggesting improved efficacy and selectivity.
The compounds show therapeutic promise for targeting cancer-specific pathways, particularly in colorectal cancer.
Abstract
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…
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Taxonomy
TopicsSynthesis and biological activity · Cancer therapeutics and mechanisms · Diverse Scientific Research Studies