Anti-cancer potentials of aervine validated through in silico molecular docking, dynamics simulations, pharmacokinetic prediction and in vitro assessment of caspase – 3 in SW480 cell line

ABSTRACT

Colon cancer is the third most lethal type of cancer in the world. Resistance to chemotherapy remains a serious barrier in the treatment of several forms of cancer, particularly colon cancer. Therefore, it is essential to develop alternative treatment methods. The docking score study of the aervine produced a low dock score for the 2BDF target compared to the 1IKN and 4OAR targets. Comparing the aervine to the reference compounds Capecitabine for 2BDF, Topotecan Hydrochloride for 1IKN and Tamoxifen for 4OAR, the binding affinity of the aervine was found to be higher. Further molecular dynamic simulation results for aervine and reference standard drugs for each cancer types reveals that aervine possess good binding affinity simulation trajectories towards all three cancer targets. The MTT assay revealed that aervine has a highest cytotoxic impact against a colorectal cancer cell line, with an IC₅₀ value of 122.12 ± 1.26µg/ ml. Aervine produces reactive oxygen species, induces caspase-3 pathway in SW480 cells, and promotes apoptosis. This research shows that aervine can be developed as a new 2BDF target inhibitor against colorectal cancer.

KEYWORDS:

• Aervine
• molecular docking
• 2BDF
• dynamic simulation
• cell line

Acknowledgements

The authors express sincere gratitude to the Department of Biotechnology, K. S. Rangasamy College of Arts and Science, Tiruchengode, Tamil Nadu, India, and the Department of Biotechnology, Sona College of Arts and Science, Salem, Tamil Nadu, India, for their technical support. Ramasamy Srinivasan, Conceptualization, Methodology, Validation, Formal analysis, Investigation, Data curation, Writing – original draft, Writing – review and editing; Desingu Kamalanathan, Conceptualization, Analysis, Data curation, Manuscript drafting, reviewing and editing; Thirumalaisamy Rathinavel, Data curation and analysis for drug likeness, ADME and molecular docking part, Manuscript reviewing and editing; Muhammad Nasir Iqbal and Gnanendra Shanmugam, Data curation and analysis for molecular dynamic simulation analysis, Manuscript reviewing and editing. All authors approve final manuscript

Disclosure statement

No potential conflict of interest was reported by the author(s).