Title

Cytotoxic Evaluation and Molecular Docking Studies of Aminopyridine Derivatives as Potential Anticancer Agents

Document Type

Article

Source of Publication

Anti-Cancer Agents in Medicinal Chemistry

Publication Date

1-1-2022

Abstract

Background: The development of resistance to available anticancer drugs is increasingly becoming a major challenge and new chemical entities could be unveiled to compensate for this therapeutic failure. Objectives: The current study demonstrated whether N-protected and deprotected amino acid derivatives of 2aminopyridine could attenuate tumor development using colorectal cancer cell lines. Methods: Biological assays were performed to investigate the anticancer potential of synthesized compounds. The in silico ADME profiling and docking studies were also performed by docking the designed compounds against the active binding site of beta-catenin (CTNNB1) to analyze the binding mode of these compounds. Four derivatives 4a, 4b, 4c, and 4d were selected for investigation of in vitro anticancer potential using colorectal cancer cell line HCT 116. The anti-tumor activities of synthesized compounds were further validated by evaluating the inhibitory effects of these compounds on the target protein beta-catenin through in vitro enzyme inhibitory assay. Results: The docking analysis revealed favorable binding energies and interactions with the target proteins. The in vitro MTT assay on colorectal cancer cell line HCT 116 and HT29 revealed potential anti-tumor activities with an IC50 range of 3.7-8.1µM and 3.27-7.7 µM, respectively. The inhibitory properties of these compounds on the concentration of beta-catenin by ELISA revealed significant percent inhibition of target protein at 100 µg/ml. Conclusion: In conclusion, the synthesized compounds showed significant anti-tumor activities both in silico and in vitro, having potential for further investigating its role in colorectal cancer.

ISSN

1871-5206

Publisher

Bentham Science Publishers Ltd.

Volume

22

Issue

14

First Page

2599

Last Page

2606

Disciplines

Medicine and Health Sciences

Keywords

2-aminopyridine, anti-tumor, beta-catenin, Colorectal cancer, heterocyclic, in silico

Scopus ID

85132308480

Indexed in Scopus

yes

Open Access

no

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