Screening the possible anti-cancer constituents of Hibiscus rosa-sinensis flower to address mammalian target of rapamycin: an in silico molecular docking, HYDE scoring, dynamic studies, and pharmacokinetic prediction

One of the most common malignancies diagnosed and the leading cause of death for cancer-stricken women globally is breast cancer. The molecular subtype affects therapy options because it is a complex disorder with multiple subtypes. By concentrating on receptor activation, mTOR (mammalian target of rapamycin) can be employed as a therapeutic target. The goal of this work was to screen a number of inhibitors produced from Hibiscus rosa-sinensis for possible target to inhibit the mTOR and to determine which has the greatest affinity for the receptor. Primarily, the ionization states of the chosen compounds were predicted using the ChemAxon web platform, and their pKa values were estimated. Given the significance of interactions between proteins in the development of drugs, structure-based virtual screening was done using AutoDock Vina. Approximately 120 Hibiscus components and ten approved anti-cancer drugs, including the mTOR inhibitor everolimus, were used in the comparative analysis. By using Lipinski's rule of five to the chosen compounds, the ADMET profile and drug-likeness characteristics were further examined to assess the anti-breast cancer activity. The compounds with the highest ranked binding poses were loaded using the SeeSAR tool and the HYDE scoring to give interactive, desolvation, and visual ΔG estimation for ligand binding affinity assessment. Following, the prospective candidates underwent three replicas of 100 ns long molecular dynamics simulations, preceded with MM-GBSA binding free energy calculation. The stability of the protein–ligand complex was determined using root mean square deviation (RMSD), root mean square fluctuation (RMSF), and protein–ligand interactions. The results demonstrated that the best mTOR binding affinities were found for stigmastadienol (107), lupeol (66), and taraxasterol acetate (111), which all performed well in comparison to the control compounds. Thus, bioactive compounds isolated from Hibiscus rosa-sinensis could serve as lead molecules for the creation of potent and effective mTOR inhibitors for the breast cancer therapy. Graphical abstract.

Medienart:	E-Artikel

Erscheinungsjahr:	2022
Erschienen:	2022

Enthalten in:	Zur Gesamtaufnahme - volume:27
Enthalten in:	Molecular diversity - 27(2022), 5 vom: 01. Nov., Seite 2273-2296

Sprache:	Englisch

Beteiligte Personen:	Rasul, Hezha O. [VerfasserIn] Aziz, Bakhtyar K. [VerfasserIn] Ghafour, Dlzar D. [VerfasserIn] Kivrak, Arif [VerfasserIn]

Links:	Volltext [lizenzpflichtig]

Themen:	Cancer MM-GBSA MTOR Molecular docking Molecular dynamic

Anmerkungen:

© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

doi:	10.1007/s11030-022-10556-9

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	SPR053189639