In Silico Analyses and Cytotoxicity Study of Asiaticoside and Asiatic Acid from Malaysian Plant as Potential mTOR Inhibitors

Molecules

SitiFadilah Abdullah¹  Idris Long²  NinieNadia Zulkipli³  Rahimah Zakaria³  TeguhHaryo Sasongko⁴  ErmaFatiha Muhammad⁵  HabibahA. Wahab⁵ 

[1] School of Dental Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Malaysia;School of Health Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Malaysia;School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Malaysia;School of Medicine, Perdana University-RCSI, Jalan MAEPS Perdana, Serdang 43400, Malaysia;School of Pharmaceutical Sciences, Universiti Sains Malaysia, Pulau Pinang 11800, Malaysia;

关键词: mammalian target of rapamycin (mTOR);    molecular docking;    everolimus;    asiaticoside;    asiatic acid;    IC₅₀;   

DOI  :  10.3390/molecules25173991

来源: DOAJ

【 摘 要 】

Natural products remain a popular alternative treatment for many ailments in various countries. This study aimed to screen for potential mammalian target of rapamycin (mTOR) inhibitors from Malaysian natural substance, using the Natural Product Discovery database, and to determine the IC₅₀ of the selected mTOR inhibitors against UMB1949 cell line. The crystallographic structure of the molecular target (mTOR) was obtained from Protein Data Bank, with Protein Data Bank (PDB) ID: 4DRI. Everolimus, an mTOR inhibitor, was used as a standard compound for the comparative analysis. Computational docking approach was performed, using AutoDock Vina (screening) and AutoDock 4.2.6 (analysis). Based on our analysis, asiaticoside and its derivative, asiatic acid, both from Centella asiatica, revealed optimum-binding affinities with mTOR that were comparable to our standard compound. The effect of asiaticoside and asiatic acid on mTOR inhibition was validated with UMB1949 cell line, and their IC₅₀ values were 300 and 60 µM, respectively, compared to everolimus (29.5 µM). Interestingly, this is the first study of asiaticoside and asiatic acid against tuberous sclerosis complex (TSC) disease model by targeting mTOR. These results, coupled with our in silico findings, should prompt further studies, to clarify the mode of action, safety, and efficacy of these compounds as mTOR inhibitors.

【 授权许可】

Unknown