Drug-likeness and 3D-QSAR Analysis of 1,2,3-triazoles as Novel Potent HIV-1 Vif Inhibitors: An approach in the development of Leads in the Treatment of HIV Infection

Olalekan Ayodele AGEDE; Louis Okeibunor Odeigah; Maryam Abimbola Jimoh; George Oche Ambrose; Olufunke Esan Olorundare

Abstract

AbstractThe human immunodeficiency virus type 1 (HIV-1) Vif protein is one of various primate lentiviral accessory proteins that act as a virulence factor to advance viral duplication and persistence. 3D quantitative structure-activity relationship (QSAR) modeling of thirty-six (36) newly discovered 1,2,3-triazole analogs as potent novel inhibitors of HIV-1 Vif to predict their biological activity (pIC50), to try to improve/optimize it using some numerical data of HIV-1 Vif inhibitors based on their physical and chemical properties (descriptors). Calculations of various 3D physicochemical properties or descriptors from structures were developed using ChemoPy descriptor software. Furthermore, according to the Kennard-Stone algorithm the dataset is divided into training set and test set. Model acceptance criteria are met due to robust internal and external validation metrics (R2train = 0.92014, adjusted R2 = 0.86309, PRESS = 0.84768, mean R2m(LOO-train) = 0.72925, Q2cv = 0.79701, R2pred = 0.67081, R2test = 0.79701). Most 1,2,3-triazole analogs exhibit good Lipinski parameter properties, with TPSA <40 indicating good permeability in biofilms and gastrointestinal absorption. The proposed model has fine robustness and predictive ability when validated by both internal and external validation. To enhance the biological activity of HIV drugs based on 1,2,3-triazole scaffolds, this model can be applied to rational drug design. Keywords: QSAR, 1,2,3-triazoles, descriptors, bioactivities, HIV, drug-likenessCitation: Olalekan Ayodele Agede, Louis Okeibunor Odeigah, Maryam Abimbola Jimoh, George Oche Ambrose, Olufunke Esan Olorundare. Drug-likeness and 3D-QSAR Analysis of 1,2,3-triazoles as Novel Potent HIV-1 Vif Inhibitors: An Approach in the Development of Leads in the Treatment of HIV Infection. Research & Reviews: A Journal of Drug Design & Discovery. 2022; 9(3): 23–37p.