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

Mathewos Anza; Milkyas Endale; Luz Cardona; Diego Cortes; Rajalakshmanan Eswaramoorthy; Jesus Zueco; Hortensia Rico; Maria Trelis; Belen Abarca

doi:10.2147/AABC.S323657

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

Adv Appl Bioinform Chem. 2021 Aug 20:14:117-132. doi: 10.2147/AABC.S323657. eCollection 2021.

Authors

Mathewos Anza¹, Milkyas Endale¹, Luz Cardona², Diego Cortes³, Rajalakshmanan Eswaramoorthy¹, Jesus Zueco⁴, Hortensia Rico⁴, Maria Trelis⁵, Belen Abarca²

Affiliations

¹ Department of Applied Chemistry, School of Applied Natural Science, Adama Science and Technology University, Adama, Ethiopia.
² Department of Organic Chemistry, Faculty of Chemistry, University of Valencia, Burjassot, Spain.
³ Department of Pharmacology, Faculty of Pharmacy, University of Valencia, Burjassot, Spain.
⁴ Department of Microbiology and Ecology, Faculty of Pharmacy, University of Valencia, Burjassot, Spain.
⁵ Parasites and Health Research Group, Department of Pharmacy, Pharmaceutical Technology and Parasitology, Faculty of Pharmacy, University of Valencia, Burjassot, Spain.

Abstract

Background: 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: ADMET; Clematis burgensis; DFT analysis; Euphorbia schimperiana; Uvaria scheffleri; antimicrobial; molecular docking.