One-Pot Synthesis and Anticancer Activity Evaluation of Indolo[1,2-a]quinoline-7-carbonitrile Derivatives
- 1Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
- 2Excellent Center for Drug Discovery, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
- 3Department of Biotechnology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
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.
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BibTeX
@article{yimnoi2026onepot,
title = {{One-Pot Synthesis and Anticancer Activity Evaluation of Indolo[1,2-a]quinoline-7-carbonitrile Derivatives}},
author = {Kredmanee Yimnoi and Norasian Boosaman and Nutthawat Chuanopparat and Kedchin Jearawuttanakul and Sawinee Seemakhan and Tanawadee Khumpanied and Warawuth Wannalo and Suparerk Borwornpinyo and Paiboon Ngernmeesri},
journal = {Molecules},
year = {2026},
month = oct,
doi = {10.3390/molecules31203731},
url = {https://www.mdpi.com/1420-3049/31/20/3731},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - One-Pot Synthesis and Anticancer Activity Evaluation of Indolo[1,2-a]quinoline-7-carbonitrile Derivatives
AU - Kredmanee Yimnoi
AU - Norasian Boosaman
AU - Nutthawat Chuanopparat
AU - Kedchin Jearawuttanakul
AU - Sawinee Seemakhan
AU - Tanawadee Khumpanied
AU - Warawuth Wannalo
AU - Suparerk Borwornpinyo
AU - Paiboon Ngernmeesri
PY - 2026
DA - 2026/10/01
JO - Molecules
DO - 10.3390/molecules31203731
UR - https://www.mdpi.com/1420-3049/31/20/3731
AB - 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.
SN - 1420-3049
ER -