| Autor: |
Deshpande SH; Department of Biotechnology, KLE Technological University, Hubballi 580031, Karnataka, India., Muhsinah AB; Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha 61441, Saudi Arabia., Bagewadi ZK; Department of Biotechnology, KLE Technological University, Hubballi 580031, Karnataka, India., Ankad GM; ICMR-National Institute of Traditional Medicine, Belagavi 590010, Karnataka, India., Mahnashi MH; Department of Pharmaceutical Chemistry, College of Pharmacy, Najran University, Najran 66462, Saudi Arabia., Yaraguppi DA; Department of Biotechnology, KLE Technological University, Hubballi 580031, Karnataka, India., Shaikh IA; Department of Pharmacology, College of Pharmacy, Najran University, Najran 66462, Saudi Arabia., Khan AA; Department of General Science, Ibn Sina National College for Medical Studies, Jeddah 21418, Saudi Arabia., Hegde HV; ICMR-National Institute of Traditional Medicine, Belagavi 590010, Karnataka, India., Roy S; ICMR-National Institute of Traditional Medicine, Belagavi 590010, Karnataka, India. |
| Abstrakt: |
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. |
