Title:Cytotoxic Evaluation and Molecular Docking Studies of Aminopyridine Derivatives
as Potential Anticancer Agents
Volume: 22
Issue: 14
Author(s): Umair Ilyas, Lina Tariq Alkury, Shagufta Naaz, Syed Aun Muhammad, Humaira Nadeem, Reem Altaf, Shahiq uz Zaman, Muhammad Faheem, Imran Sajid, Mohsin Tasawar Cheema, Abdul Mannan, Fawad Ali Shah*Shupeng Li*
Affiliation:
- Department of Pharmacology, Faculty
of Pharmaceutical Sciences, Riphah International University, Islamabad-44000, Pakistan
- State Key Laboratory of Oncogenomics, School of Chemical Biology and
Biotechnology, Peking University Shenzhen, Shenzhen China
Keywords:
Colorectal cancer, 2-aminopyridine, heterocyclic, in silico, beta-catenin, anti-tumor.
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 2-
aminopyridine 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.
