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Current Drug Discovery Technologies

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ISSN (Print): 1570-1638
ISSN (Online): 1875-6220

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Research Article

Synthesis, Cytotoxicity Evaluation and Molecular Docking of Fluorine Containing Hexahydroquinoline-3-Carbonitrile Derivatives

Author(s): Nishith Teraiya*, Subhas S. Karki and Ashlesha Chauhan

Volume 19, Issue 1, 2022

Published on: 29 December, 2020

Article ID: e140122189603 Pages: 11

DOI: 10.2174/1570163817666201229154848

Price: $65

Abstract

Background: Fluorine containing hexahydroquinoline-3-carbonitrile derivatives were found to have potent cytotoxicity. Furthermore, fluorine can modulate pharmacokinetic and pharmacodynamic profile of drugs. Hence, new derivatives containing fluorine were explored as potential cytotoxic agents.

Objective: Difluoro substituted compounds containing aromatic/heteroaromatic rings were designed, synthesized and screened for in vitro cytotoxicity on cancer cell lines. The active compounds were subjected to docking on Mcl-1 and ADME/T prediction.

Methods: The synthesized compounds were characterized using various spectral techniques like FT-IR, 1H NMR, 13C NMR and Mass spectra. Compounds were screened for cytotoxicity on NCI-60 cell lines at the National Cancer Institute. The active compounds were evaluated additionally by MTT and SRB assay.

Results: Compounds (6l and 6o) showed maximum cytotoxicity with (% GI) of 69 and 63.7 at 10 μM drug concentration, respectively. Compound 6i showed potent cytotoxicity with GI50 of 7.2 μM against Ishikawa cell line. Compound 6o was nearly as active as a reference with IC50 of 9.39 μM and 13.54 μM against HT-29 and HCT-116, respectively, and compound 6l also showed equal potency to that of reference with IC50 of 9.66 μM against Caco-2. Compounds 6i, 6o and 6l showed high docking scores, suggesting their cytotoxicity. Furthermore, ADME/T prediction revealed that all the compounds had drug-likeness properties.

Conclusion: Enhanced lipophilic interaction of compounds due to the presence of fluorine in compounds 6i and 6l was revealed during the docking study. Compound 6i can be explored as a lead molecule against other endometrial cancer in futuristic drug development.

Keywords: Hexahydroquinoline-3-carbonitrile derivatives, cytotoxicity, NCI-60 cell lines, MTT assay, docking, venetoclax, imatinib.

Graphical Abstract

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