Molecular Docking of Natural Alkaloids with Bcl-xL Protein in The Apoptosis Process

Noraziah Nordin; Wan Noraini Wan Sulaiman; Marjanu Hikmah Elias

doi:10.33102/mjosht.v10i2.406

Authors

Noraziah Nordin Department of Basic Medical Sciences 1, Faculty of Medicine & Health Sciences, Universiti Sains Islam Malaysia, 71800, Nilai, Negeri Sembilan, Malaysia.
Wan Noraini Wan Sulaiman Department of Basic Medical Sciences 1, Faculty of Medicine & Health Sciences, Universiti Sains Islam Malaysia, 71800, Nilai, Negeri Sembilan, Malaysia. https://orcid.org/0000-0003-2758-2074
Marjanu Hikmah Elias Department of Basic Medical Sciences 1, Faculty of Medicine & Health Sciences, Universiti Sains Islam Malaysia, 71800, Nilai, Negeri Sembilan, Malaysia.

DOI:

https://doi.org/10.33102/mjosht.v10i2.406

Keywords:

Bcl-xL protein, Alkaloids, Docking, AutoDock Vina, cancer chemotherapy

Abstract

Background: The anti-apoptotic protein Bcl-xL is a viable target for cancer therapy due to its critical role in cancer formation and resistance to chemotherapy. Insights into Bcl-xL’s role have spurred the development of a new category of cancer drugs called Bcl-xL inhibitors, which mimic the BH3-only protein to cause apoptosis. It could be initiated using alkaloids, owing to their remarkable biological characteristics. Alkaloids, among the biggest obtainable from plants, possess a distinctive structure characterized by the presence of a nitrogen atom in various positions within the molecule. Objective: In the current study, the potential of various alkaloids as Bcl-xL inhibitors was investigated through a molecular docking study. Methods: AutoDock Vina software was used to perform docking simulations of the alkaloids. Results: Ten alkaloids/Bcl-xL protein complexes demonstrated strong binding affinities less than -8.0 kcal/mol^-1. These complexes include phaenthine (26), 4,5-Dioxoaporphine (1), anonaine (2), atherospermidine (4), limacine (14), liriodenine (16), monomargine (18), ouregidione (24), oxostephanine (25), and taliscanine (29) as the ligand of Bcl-xL protein. Notably, the complexes of Bcl-xL/dicentrinone (10), ouregidione (24), stepharine (28), and taliscanine (29) displayed three to four hydrogen bonds along with hydrophobic contacts. Conclusion: These results suggest that certain alkaloids could act as potential Bcl-xL inhibitors, mimicking BH3-only proteins and thereby potentially triggering apoptosis during cancer treatment.

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