Publications by authors named "Milkyas Endale"

7 Publications

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Antibacterial and antioxidant activities of extracts and isolated compounds from the roots extract of Cucumis prophetarum and in silico study on DNA gyrase and human peroxiredoxin 5.

BMC Chem 2021 May 6;15(1):32. Epub 2021 May 6.

Department of Applied Chemistry, School of Applied Natural Science, Adama Science and Technology University, P.O.Box 1888, Adama, Ethiopia.

Background: Cucumis prophetarum is traditionally used to treat liver and lung disorders, heart failure, diarrhea, gonorrhea, skin infections, intestinal problems and cancer. In the present work, the isolation of two novel compounds along with their antibacterial and antioxidant activities is reported for the first time.

Methods: Silica gel column chromatography was applied to separate constituents of the roots of C. prophetarum. The structures of isolated compounds were established using H NMR, C NMR, DEPT-135, COSY, HSQC and HMBC. Agar well diffusion, DPPH assay and ferric thiocyante methods were used for antibacterial, radical scavenging and anti-lipid peroxidation activities, respectively. AutoDock Vina open source program was used for molecular docking analysis.

Results: Evaluation of the in vitro antibacterial activity of the constituents against S. aureus, B. subtilis, E. coli and S. thyphimurium revealed that the hexane extract were active against E. coli with IZ of 15.0 ± 1.41 mm, whereas an IZ of 14.6 ± 1.70 mm for MeOH extract was observed against S. aureus. Compound 1 displayed IZ of 13.6 ± 0.94 mm against E. coli and curcurbiatin 2 showed activity against B. subtilis with IZ of 13.3 ± 0.54 mm. The molecular docking analysis showed that cucurbitacins 2 and 3 have binding energy of -6.7 and -6.9 kcal/mol, respectively. The methanol and the hexane extracts of the roots of C. prophetarum inhibited DPPH radical by 70.4 and 63.3% at 100 µg/mL, respectively. On the other hand, the methanol extract inhibited lipid peroxidation by 53.0%.

Conclusion: The present study identified five compounds from the root extracts of C. prophetarum, of which two are novel cucurbitacins (1, 2). The in vitro antibacterial activity of the hexane and methanol extracts was better than the activity displayed by the isolated compounds. This is probably due to the synergistic effects of the constituents present in the root extract. The in silico molecular docking study results showed that, compounds 2 and 3 have minimum binding energy and have good affinity toward the active pocket, thus, they may be considered as good inhibitor of DNA gyrase B. Furthermore, the "drug-likeness" and ADMET prediction of compounds 2-5 nearly showed compliance with the Lipinski rule, with good absorption, distribution, metabolism, and excretion generally. The radical scavenging and anti-lipid peroxidation activities of the extracts were better than the isolated compounds. This is attributed to the presence of phenolics and flavonoids as minor constituents in the extracts of these species. Therefore, the in vitro antibacterial activity and molecular docking analysis suggest the potential use of the isolated compounds as medicine which corroborates the traditional use of the roots of C. prophetarum.
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http://dx.doi.org/10.1186/s13065-021-00758-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103605PMC
May 2021

In silico Molecular Docking, DFT Analysis and ADMET Studies of Carbazole Alkaloid and Coumarins from Roots of : A Potent Inhibitor for Quorum Sensing.

Adv Appl Bioinform Chem 2021 5;14:13-24. Epub 2021 Feb 5.

Department of Applied Chemistry, School of Applied Natural Science, Adama Science and Technology University, Adama, 1888, Ethiopia.

Introduction: In modern drug design, in silico methods are largely used to understand drug-receptor interactions and quantum chemical properties. In the present study, a computational de novo design approach was used to confirm mode of binding for antibacterial activity, elucidating quantum chemical properties and ADMET-drug-likeness of carbazole alkaloid () and three coumarins (-) isolated from roots of .

Methods: Docking studies were performed with DNA-Gyrase (6F86) and LasR binding domain (2UV0) employing a flexible ligand docking approach using AutoDock Vina. SwissADME prediction and toxicological predictions were performed by ADMET. The optimized structures and molecular electrostatic potential surface of the isolated compounds were predicted by DFT analysis using B3LYP/6-31G basis levels.

Results And Discussion: The docking results revealed that compound showed better docking scores against both DNA gyrase B and LasR binding domain compared with ciprofloxacin with potential as an inhibitor of bacterial DNA gyrase and quorum sensing LasR binding domain. The SwissADME prediction results showed that all the isolated compounds () satisfy Lipinski's rule of five with zero violations. Toxicological prediction results suggested that all compounds and ciprofloxacin are non-hepatotoxic, non-carcinogenic, non-irritant, immunogenic, and non-cytotoxic. The DFT analysis results revealed that compound has large electronegativity (χeV), global softness (σ eV), global electrophilicity (ωeV), and mutagenicity value closer to ciprofloxacin (with LD value of 480 mg/kg) suggesting better bioactivity and chemical reactivity with considerable intra-molecular charge transfer between electron-donor to electron-acceptor groups.

Conclusion: Overall, compound may serve as a lead molecule that could be developed into a potent DNA gyrase B inhibitor and efficient inhibitor for quorum sensing auto-inducer LasR binding domain of .
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http://dx.doi.org/10.2147/AABC.S290912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875078PMC
February 2021

Antibacterial Activity of Coumarins and Carbazole Alkaloid from Roots of .

Adv Pharmacol Sci 2019 3;2019:5419854. Epub 2019 Feb 3.

Department of Applied Chemistry, Adama Science and Technology University, P.O.Box 1888, Adama, Ethiopia.

is one of the medicinal plants used traditionally for treatment of parasitic infections, irritation (boils, ringworm, and eczema), flatworm infestations, influenza, abdominal cramps, and constipation. Phytochemical screening test of dichloromethane/methanol (1 : 1) roots extract revealed the presence of flavonoids, phytosterols, coumarins, phenols, alkaloids, tannins, terpenoids, and free reducing sugars and the absence of saponins. Silica gel column chromatographic separation of the dichloromethane/methanol (1 : 1) extract afforded a carbazole alkaloid derivative of heptazoline () and three coumarins (-), including the known coumarins imperatorin () and chalepin (). Structures of the compounds were elucidated by spectroscopic techniques (IR, H NMR, C NMR, and DEPT-135). Antibacterial activity of the crude extracts and isolated compounds was screened using agar diffusion method against strains of , , , and . The results of antibacterial test revealed derivative of heptaphylline () and imperatorin () exhibited comparable antibacterial activity against and (14 and 13 mm zone of inhibition, respectively) to that of ciprofloxacin (15 mm zone of inhibition) at a concentration of 20 g/mL. Chalepin () revealed more antibacterial activity against (16 mm zone of inhibition) compared to ciprofloxacin (15 mm).
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http://dx.doi.org/10.1155/2019/5419854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6378073PMC
February 2019

Antibacterial Activity of Two Flavans from the Stem Bark of .

Adv Pharmacol Sci 2018 30;2018:5870161. Epub 2018 Apr 30.

Applied Chemistry Program, School of Applied Natural Science, Adama Science and Technology University, P.O. Box 1888, Adama, Ethiopia.

Vatke is one of the medicinal plants used traditionally for treatment of intestinal tape worm, dysmenorrheal, bacterial, and fungal infections. Phytochemical screening test of the dichloromethane/methanol (1 : 1) and methanol extracts revealed the presence of phenols, alkaloids, tannins, and flavonoids whereas terpenoids, glycoside, and phytosterols were absent. Silica gel column chromatographic separation of the methanol extract afforded 3,5,7,3',4'-pentahydroxyflavan, named epicatechin (), along with a close flavan derivative (). Structures of the compounds were elucidated by spectroscopic techniques (1D and 2D NMR, FTIR, and UV-Vis). The crude extracts and isolated compounds were screened for antibacterial activity against strains of , , , , and . Epicatechin () exhibited comparable antibacterial activity against and (15 and 12 mm zone of inhibition, resp.) to that of the control antibiotic gentamicin, with zone of inhibition of 15 and 12 mm, respectively, at a concentration of 20 g/mL.
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http://dx.doi.org/10.1155/2018/5870161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5952501PMC
April 2018

Anthraquinones of the roots of Pentas micrantha.

Molecules 2012 Dec 27;18(1):311-21. Epub 2012 Dec 27.

Department of Chemistry, University of Nairobi, P.O. Box 30197-00100, Nairobi, Kenya.

Pentas micrantha is used in the East African indigenous medicine to treat malaria. In the first investigation of this plant, the crude methanol root extract showed moderate antiplasmodial activity against the W2- (3.37 μg/mL) and D6-strains (4.00 μg/mL) of Plasmodium falciparum and low cytotoxicity (>450 μg/mL, MCF-7 cell line). Chromatographic separation of the extract yielded nine anthraquinones, of which 5,6-dihydroxylucidin-11-O-methyl ether is new. Isolation of a munjistin derivative from the genus Pentas is reported here for the first time. The isolated constituents were identified by NMR and mass spectrometric techniques and showed low antiplasmodial activities.
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http://dx.doi.org/10.3390/molecules18010311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6270246PMC
December 2012

Busseihydroquinones A-D from the roots of Pentas bussei.

J Nat Prod 2012 Jul 18;75(7):1299-304. Epub 2012 Jun 18.

Department of Chemistry, University of Nairobi , P.O. Box 30197-00100, Nairobi, Kenya.

Four new naphthohydroquinones, named busseihydroquinones A-D (1-4), along with a known homoprenylated dihydronaphthoquinone (5), were isolated from the CH(2)Cl(2)/MeOH (1:1) extract of the roots of Pentas bussei. Although the genus Pentas is frequently used by traditional healers for the treatment of malaria, only marginal activities against the chloroquine-sensitive (D6) and the chloroquine-resistant (W2) strains of Plasmodium falciparum were observed for the crude root extract and the isolated constituents of this plant.
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http://dx.doi.org/10.1021/np3002223DOI Listing
July 2012

Antiplasmodial quinones from Pentas longiflora and Pentas lanceolata.

Planta Med 2012 Jan 6;78(1):31-5. Epub 2011 Oct 6.

Department of Chemistry, University of Nairobi, Nairobi, Kenya.

The dichloromethane/methanol (1:1) extracts of the roots of Pentas longiflora and Pentas lanceolata showed low micromolar (IC(50) = 0.9-3 µg/mL) IN VITRO antiplasmodial activity against chloroquine-resistant (W2) and chloroquine-sensitive (D6) strains of PLASMODIUM FALCIPARUM. Chromatographic separation of the extract of PENTAS LONGIFLORA led to the isolation of the pyranonaphthoquinones pentalongin (1) and psychorubrin (2) with IC(50) values below 1 µg/mL and the naphthalene derivative mollugin (3), which showed marginal activity. Similar treatment of Pentas lanceolata led to the isolation of eight anthraquinones ( 4-11, IC(50) = 5-31 µg/mL) of which one is new (5,6-dihydroxydamnacanthol, 11), while three--nordamnacanthal (7), lucidin-ω-methyl ether (9), and damnacanthol (10)--are reported here for the first time from the genus Pentas. The compounds were identified by NMR and mass spectroscopic techniques.
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http://dx.doi.org/10.1055/s-0031-1280179DOI Listing
January 2012