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.
DOI Link
ISSN
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
Recommended Citation
Ilyas, Umair; Alkury, Lina Tariq; Naaz, Shagufta; Muhammad, Syed Aun; Nadeem, Humaira; Altaf, Reem; Uz Zaman, Shahiq; Faheem, Muhammad; Sajid, Imran; Cheema, Mohsin Tasawar; Mannan, Abdul; Shah, Fawad Ali; and Li, Shupeng, "Cytotoxic Evaluation and Molecular Docking Studies of Aminopyridine Derivatives as Potential Anticancer Agents" (2022). All Works. 5263.
https://zuscholars.zu.ac.ae/works/5263
Indexed in Scopus
yes
Open Access
no