Authors
Kredmanee Yimnoi, Norasian Boosaman, Nutthawat Chuanopparat, Kedchin Jearawuttanakul, Sawinee Seemakhan, Tanawadee Khumpanied, Warawuth Wannalo, Suparerk Borwornpinyo, Paiboon Ngernmeesri
Published in
Molecules (Basel, Switzerland). Volume 31. Issue 20. Oct 17, 2026. Epub Oct 17, 2026.
Abstract
Indolo[1,2-a]quinoline derivatives represent an attractive heterocyclic scaffold in anticancer drug discovery. Herein, fifty-four novel indolo[1,2-a]quinoline-7-carbonitrile analogs were synthesized via a transition-metal-free cascade reaction involving nucleophilic aromatic substitution and Knoevenagel condensation, affording yields up to 87%. All compounds were evaluated for their antiproliferative activities against human colorectal (HCT-116 and HT-29) and breast (MCF-7) cancer cell lines using the MTT assay. Eleven analogs exhibited high potency with IC50 values ranging from 2.16 to 8.18 µM. Notably, 2-bromoindolo[1,2-a]quinoline-7-carbonitrile displayed broad-spectrum cytotoxicity across HCT-116, HT-29, and MCF-7 lines (IC50 = 3.64 ± 0.72, 5.29 ± 1.83, and 6.06 ± 0.16 µM, respectively). To explore potential binding modes and rationalize structural features, molecular docking simulations were conducted against CDK2, CDK6, and EGFR kinase models. The in silico results revealed strong predicted binding affinities (-7.73 to -9.49 kcal/mol), driven predominantly by C7-cyano hydrogen bonding and hydrophobic interactions, providing hypothetical insights into how these scaffolds might interact with ATP-binding pockets. These findings demonstrate that the indolo[1,2-a]quinoline-7-carbonitrile framework holds significant promise as a pharmacophore for further mechanistic and drug development studies.
PMID:
42943799
Bibliographic data and abstract were imported from PubMed on 27 Oct 2026.
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