In vitroantimicrobial, physicochemical, pharmacokinetics and molecular docking studies of benzoyl uridine esters against SARS-CoV-2 main protease

Abstract

Different esters were found potential against microorganisms, and could be a better choice to solve the multidrug resistant (MDR) pathogenic global issue due to their improved biological and pharmacokinetic properties. In this view, several 4- t -butylbenzoyl uridine esters 4–15 with different aliphatic and aromatic groups were synthesized for antimicrobial, physicochemical and biological studies. In vitro antimicrobial tests against nine bacteria and three fungi along with prediction of activity spectra for substances (PASS) indicated promising antifungal functionality of these uridine esters compared to the antibacterial activities. In support of this observation their cytotoxicity and molecular docking studies have been performed against lanosterol 14α-demethylase (CYP51A1) and Aspergillus flavus (1R51). Significant binding affinities were observed against SARS-CoV-2 main protease (7BQY) considering hydroxychloroquine (HCQ) as standard. ADMET predictions were investigated to evaluate their absorption, metabolism and toxic properties. Most of the uridine esters showed better results than that of the HCQ. Overall, the present study might be useful for the development of uridine-based novel MDR antimicrobial and COVID-19 drugs.

The effects of protecting and acyl groups on the conformation of benzyl α-L-rhamnopyranosides: An in silico study

“…For the present study we have considered two series of esters of benzyl α-L-rhamnopyranoside (3). The first series (4-6 and 7a,b) were prepared via 2,3-Oacetonide protection of compound 3 (Figure 2) [41]. The second series (8 and 9a-d) were prepared using dibutyltin oxide method (Figure 2) [42].…”

“…The second series (8 and 9a-d) were prepared using dibutyltin oxide method (Figure 2) [42]. All these benzyl rhamnopyranosides 4-9 were characterized by spectroscopic technique and elemental analyses, and their antimicrobial activities were also reported [27,41].…”

Antimicrobial Activity, in silico Molecular Docking, ADMET and DFT Analysis of Secondary Metabolites from Roots of Three Ethiopian Medicinal Plants

“…The DFT optimized structures were used as input for AutoDock Vina, in order to carry out the docking simulation. [15][16][17] The crystal structure of receptor molecule E. coli gyrase B (PDB ID: 6F86), and human topoisomerase II alpha (PDB ID: 3QX3) were downloaded from protein data bank. The protein preparation was done using the reported standard protocol 18 by removing the cocrystallized ligand, selected water molecules and cofactors, the target protein file was prepared by leaving the associated residue with protein by using auto preparation of target protein file Auto Dock 4.2 (MGL tools1.5.7).…”

“…22 In the present study, the DFT analysis of compounds (1, 3-5) was performed using Gaussian 09 and visualized through Gauss view 6.0. [15][16][17] The structural coordinates were optimized using B3LYP/6-31 G (d,p) level basis set without any symmetrical constraints. The molecular electrostatic potential map and energies of the compounds were obtained from the optimized geometry.…”

<i>In Silico</i> Biological Profile Prediction of Some Selectively Synthesized Acyl Rhamnopyranosides

“…In addition to their uses as detergent and cosmetic products, some SEs are used in the food, pharmaceutical, detergent, agricultural, fine chemical, and personal care industries considering their suitable insecticidal and antimicrobial activities [7][8][9]. Recently, Matin et al [10] reported the synthesis of several uridine-based SEs and observed that the sugar ester part(s) of uridines (1, Fig. 1) is more potent against SARS-CoV-2 main protease (Mpro; 7BQY) as compared to the traditional drug hydroxychloroquine (HCQ).…”