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In the present work, the isolation of two novel compounds along with their antibacterial and antioxidant activities is reported for the first time.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Silica gel column chromatography was applied to separate constituents of the roots of<jats:italic>C. prophetarum.<\/jats:italic>The structures of isolated compounds were established using<jats:sup>1<\/jats:sup>H NMR,<jats:sup>13<\/jats:sup>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Evaluation of the in vitro antibacterial activity of the constituents against<jats:italic>S. aureus, B. subtilis, E. coli<\/jats:italic>and<jats:italic>S. thyphimurium<\/jats:italic>revealed that the hexane extract were active against<jats:italic>E. coli<\/jats:italic>with IZ of 15.0\u2009\u00b1\u20091.41\u00a0mm, whereas an IZ of 14.6\u2009\u00b1\u20091.70\u00a0mm for MeOH extract was observed against<jats:italic>S. aureus<\/jats:italic>. Compound<jats:bold>1<\/jats:bold>displayed IZ of 13.6\u2009\u00b1\u20090.94\u00a0mm against<jats:italic>E. coli<\/jats:italic>and curcurbiatin<jats:bold>2<\/jats:bold>showed activity against<jats:italic>B. subtilis<\/jats:italic>with IZ of 13.3\u2009\u00b1\u20090.54\u00a0mm. The molecular docking analysis showed that cucurbitacins<jats:bold>2<\/jats:bold>and<jats:bold>3<\/jats:bold>have binding energy of -6.7 and -6.9\u00a0kcal\/mol, respectively. The methanol and the hexane extracts of the roots of<jats:italic>C. prophetarum<\/jats:italic>inhibited DPPH radical by 70.4 and 63.3% at 100\u00a0\u00b5g\/mL, respectively. On the other hand, the methanol extract inhibited lipid peroxidation by 53.0%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The present study identified five compounds from the root extracts of<jats:italic>C. prophetarum<\/jats:italic>, of which two are novel cucurbitacins (<jats:bold>1<\/jats:bold>,<jats:bold>2<\/jats:bold>). 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<jats:bold>2<\/jats:bold>and<jats:bold>3<\/jats:bold>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 \u201cdrug-likeness\u201d and ADMET prediction of compounds<jats:bold>2\u20135<\/jats:bold>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<jats:italic>C. prophetarum<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s13065-021-00758-x","type":"journal-article","created":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T18:03:49Z","timestamp":1620324229000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["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"],"prefix":"10.1186","volume":"15","author":[{"given":"Wario","family":"Galma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milkyas","family":"Endale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emebet","family":"Getaneh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajalakshmanan","family":"Eswaramoorthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Temesgen","family":"Assefa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yadessa","family":"Melaku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,6]]},"reference":[{"key":"758_CR1","first-page":"562","volume":"14","author":"SO Chung","year":"2015","unstructured":"Chung SO, Kim YJ, Park SU (2015) An updated review of cucurbitacins and their biological and pharmacological activities. 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