Title of article :
Antimicrobial Activity, in silico Molecular Docking, ADMET and DFT Analysis of Secondary Metabolites from Roots of Three Ethiopian Medicinal Plants
Author/Authors :
Anza, Mathewos Department of Applied Chemistry - School of Applied Natural Science - Adama Science and Technology University, Adama, Ethiopia , Endale, Milkyas Department of Applied Chemistry - School of Applied Natural Science - Adama Science and Technology University, Adama, Ethiopia , Cardona, Luz Department of Organic Chemistry - Faculty of Chemistry - University of Valencia, Burjassot, Spain , Cortes, Diego Department of Pharmacology - Faculty of Pharmacy - University of Valencia, Burjassot, Spain , Eswaramoorthy, Rajalakshmanan Department of Applied Chemistry - School of Applied Natural Science - Adama Science and Technology University, Adama, Ethiopia , Zueco, Jesus Department of Organic Chemistry - Faculty of Chemistry - University of Valencia, Burjassot, Spain , Rico, Hortensia Department of Organic Chemistry - Faculty of Chemistry - University of Valencia, Burjassot, Spain , Trelis, Maria Department of Organic Chemistry - Faculty of Chemistry - University of Valencia, Burjassot, Spain , Abarca, Belen Department of Pharmacology - 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 tradi-
tional uses of studied plants
Keywords :
Uvaria scheffleri , Clematis burgensis , Euphorbia schimperiana , antimicrobial , molecular docking , ADMET , DFT analysis
