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

• Main Authors: Anza M, Endale M, Cardona L, Cortes D, Eswaramoorthy R, Zueco J, Rico H, Trelis M, Abarca B
• Format: Article
• Language: English
• Published: Dove Medical Press 2021-08-01
• Series: Advances and Applications in Bioinformatics and Chemistry
• Subjects: uvaria scheffleri; clematis burgensis; euphorbia schimperiana; antimicrobial; molecular docking; admet; dft analysis
• Online Access: https://www.dovepress.com/antimicrobial-activity-in-silico-molecular-docking-admet-and-dft-analy-peer-reviewed-fulltext-article-AABC

Mathewos Anza,1 Milkyas Endale,1 Luz Cardona,2 Diego Cortes,3 Rajalakshmanan Eswaramoorthy,1 Jesus Zueco,4 Hortensia Rico,4 Maria Trelis,5 Belen Abarca2 1Department of Applied Chemistry, School of Applied Natural Science, Adama Science and Technology University, Adama, Ethiopia; 2Department of Organic Chemistry, Faculty of Chemistry, University of Valencia, Burjassot, Spain; 3Department of Pharmacology, Faculty of Pharmacy, University of Valencia, Burjassot, Spain; 4Department of Microbiology and Ecology, Faculty of Pharmacy, University of Valencia, Burjassot, Spain; 5Parasites and Health Research Group, Department of Pharmacy, Pharmaceutical Technology and Parasitology, Faculty of Pharmacy, University of Valencia, Burjassot, SpainCorrespondence: Mathewos Anza; Milkyas EndaleDepartment of Applied Chemistry, School of Applied Natural Science, Adama Science and Technology University, P.O. Box 1888, Adama, EthiopiaEmail [e-mail]; [e-mail]: Uvaria scheffleri (Annonaceae), Clematis burgensis (Ranunculaceae), and Euphorbia schimperiana (Euphorbiaceae) are medicinal plants traditionally used to treat cough, tuberculosis, asthma, sore throat and skin infections.Methods: Silica gel column chromatographic separation was used to isolate compounds. Crude extract and isolated compounds were evaluated for antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans via the broth dilution method. Docking studies were performed with E. coli DNA-Gyrase B and human DNA topoisomerase IIα by using AutoDock Vina. ADMET were predicted by SwissADME, PreADMET, and OSIRIS Property predictions. The optimized structures and molecular electrostatic potential surface of the isolated compounds were predicted by DFT analysis using B3LYP/6-31G basis levels.Results: Silica gel column chromatographic separation afforded five compounds 1– 5 of which N-methyl-2,3-bis(2-hydroxybenzyl)-1Н-indol ( 1) is reported herein for the first time, along with known C-benzylated dihydrochalcone uvaretin ( 2), bis(2-ethylheptyl) phthalate ( 3), lupeol ( 4) and suberosin derivative ( 5). Dichloromethane roots extract of U. scheffleri showed potent antibacterial activity against S. aureus (MIC = 6.25 μg/mL) compared to gentamicin (MIC=5 μg/mL). In silico, molecular docking analysis of compounds ( 1and 3– 5) showed strong interaction with E. coli DNA gyrase B with a binding energy value ranging from − 6.9 to − 6.0 kcal/mol compared to ciprofloxacin − 7.2 kcal/mol, whereas analysis against human topoisomerase IIα showed binding energy value ranging from − 5.9 to − 5.3 kcal/mol compared to vosaroxin (− 6.2 kcal/mol).Conclusion: The results obtained suggest that N-methyl-2,3-bis(2-hydroxybenzyl)-1Н-indol ( 1) and coumarin ( 5) are potential topoisomerase II α inhibitors and might be used as anticancer agents. The ADMET studies showed the highest drug-likeness properties for studied compounds other than bis(2-ethylheptyl) phthalate ( 3). DFT calculations suggested that studied compounds showed the lowest gap energy and were chemically reactive, and isolated compounds may serve as potential drug candidates that corroborate with the traditional uses of studied plants.Keywords: Uvaria scheffleri, Clematis burgensis, Euphorbia schimperiana, antimicrobial, molecular docking, ADMET, DFT analysis