In Silico Study on the Interactions, Molecular Docking, Dynamics and Simulation of Potential Compounds from Withania somnifera (L.) Dunal Root against Cancer by Targeting KAT6A

by Selleckchem | Jan 01 2024

Cancer is characterized by the abnormal development of cells that divide in an uncontrolled manner and further take over the body and destroy the normal cells of the body. Although several therapies are practiced, the demand and need for new therapeutic agents are ever-increasing because of issues with the safety, efficacy and efficiency of old drugs. Several plant-based therapeutics are being used for treatment, either as conjugates with existing drugs or as standalone formulations. Withania somnifera (L.) Dunal is a highly studied medicinal plant which is known to possess immunomodulatory activity as well as anticancer properties. The pivotal role of KAT6A in major cellular pathways and its oncogenic nature make it an important target in cancer treatment. Based on the literature and curated datasets, twenty-six compounds from the root of W. somnifera and a standard inhibitor were docked with the target KAT6A using Autodock vina. The compounds and the inhibitor complexes were subjected to molecular dynamics simulation (50 ns) using Desmond to understand the stability and interactions. The top compounds (based on the docking score of less than -8.5 kcal/mol) were evaluated in comparison to the inhibitor. Based on interactions at ARG655, LEU686, GLN760, ARG660, LEU689 and LYS763 amino acids with the inhibitor WM-8014, the compounds from W. somnifera were evaluated. Withanolide D, Withasomniferol C, Withanolide E, 27-Hydroxywithanone, Withanolide G, Withasomniferol B and Sitoindoside IX showed high stability with the residues of interest. The cell viability of human breast cancer MCF-7 cells was evaluated by treating them with W. Somnifera root extract using an MTT assay, which showed inhibitory activity with an IC50 value of 45 µg/mL. The data from the study support the traditional practice of W. somnifera as an anticancer herb.

Comments:

It seems like you've summarized a comprehensive study on the potential anticancer properties of Withania somnifera (Ashwagandha) and its compounds. The research explored the docking and molecular dynamics simulation of compounds from W. somnifera with KAT6A, highlighting their potential interactions and stability. Additionally, the study included an evaluation of these compounds in comparison to a standard inhibitor, demonstrating their potential efficacy.

The identification of compounds like Withanolide D, Withasomniferol C, Withanolide E, 27-Hydroxywithanone, Withanolide G, Withasomniferol B, and Sitoindoside IX that exhibit stability and interactions with specific amino acids linked to KAT6A is promising. Moreover, the study's inclusion of cell viability assays using MCF-7 cells further supports the potential anticancer effects of W. somnifera.

This research underscores the significance of plant-based therapies and traditional practices in developing new therapeutic agents for cancer treatment. The multi-pronged approach involving molecular simulations, identification of compounds, and in vitro assays provides a strong foundation for further exploration and development of these natural compounds as potential anticancer agents.