In Silico Pharmacokinetics, ADMET Study and Conceptual DFT Analysis of Two Plant Cyclopeptides Isolated From Rosaceae as a Computational Peptidology Approach.

Norma Flores-Holguín,Daniel Glossman-Mitnik,Juan Frau

doi:10.3389/fchem.2021.708364

Abstract

This research presents the outcomes of a computational determination of the chemical reactivity and bioactivity properties of two plant cyclopeptides isolated from Rosaceae through the consideration of Computational Peptidology (CP), a protocol employed previously in the research of similar molecular systems. CP allows the prediction of the global and local descriptors that are the integral foundations of Conceptual Density Functional Theory (CDFT) and which could help in getting in the understanding of the chemical reactivity properties of the two plant cyclopeptides under study, hoping that they could be related to their bioactivity. The methodology based on the Koopmans in DFT (KID) approach and the MN12SX/Def2TZVP/H2O model chemistry has been successfully validated. Various Chemoinformatics tools have been used to improve the process of virtual screening, thus identifying some additional properties of these two plant cyclopeptides connected to their ability to behave as potentially useful drugs. With the further objective of analyzing their bioactivity, the CP protocol is complemented with the estimation of some useful parameters related to pharmacokinetics, their predicted biological targets, and the Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) parameters related to the bioavailability of the two plant cyclopeptides under study are also reported.

Highlights

Plant-based bioactive compounds have drawn attention of all communities around the world due to their unique biochemical activities and health benefits
A Webtool named SwissTargetPrediction for efficient prediction of protein targets of small molecules has been considered for the determination of the potential bioactivity of the two terrestrial plant cyclopeptides considered in this study (Daina et al, 2019)
Some ADME parameters were estimated with the aid of Chemicalize and the online available SwissADME software (Daina et al, 2017).Additional information about the Pharmacokinetics parameters and the ADMET properties were obtained by resorting to pkCSM (Pires et al, 2015), a software for the prediction of small-molecule pharmacokinetic properties using SMILES

Summary

Introduction

Plant-based bioactive compounds have drawn attention of all communities around the world due to their unique biochemical activities and health benefits. Research studies have confirmed the safeguarding effects of certain plant-based diets on cardiovascular diseases, obesity, cancer, diabetes, etc. (Guha et al, 2021). Plant-based drugs from secondary metabolites constitute more than 25% of approved new drugs during last 30 years. 50% of the commercially successful medicinal components were developed based on knowledge from plant secondary metabolites and their structures (Chaudhari and Chakraborti, 2021). Bioactive peptides are organic substances formed by amino acids joined by covalent bonds known as amide or peptide bonds. Peptides can exist free in terrestrial plants and marine sources, the vast majority of known bioactive peptides are enclosed within the structure

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