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It effectively inhibited vascular endothelial growth factor receptor\u20102 (VEGFR\u20102) with an IC<jats:sub>50<\/jats:sub> value of 0.082\u2009\u00b1\u20090.004\u2009\u00b5M compared with sorafenib. While compound <jats:bold>3e<\/jats:bold> significantly downregulated total VEGFR\u20102 and its phosphorylation, it markedly reduced the HUVEC's migratory potential, resulting in a significant disruption in wound healing. Furthermore, compound <jats:bold>3e<\/jats:bold> caused a 22.51\u2010fold increment in total apoptotic level in leukemia cell line HL\u201060(TB) and a 6.91\u2010fold increase in the caspase\u20103 level. Compound <jats:bold>3e<\/jats:bold> also caused cell cycle arrest, mostly at the G1\/S phase. Antibacterial activity was evaluated against Gram\u2010positive a70am\u2010negative bacterial strains. Compound <jats:bold>3b<\/jats:bold> was the most active derivative, with the same minimum inhibitory concentration and minimum bactericidal concentration value of 128\u2009\u03bcg\/mL against <jats:italic>K. pneumonia<\/jats:italic> and high stability in mammalian plasma. Moreover, compounds <jats:bold>3b<\/jats:bold> and <jats:bold>3f<\/jats:bold> inhibited Gram\u2010negative DNA gyrase with IC<jats:sub>50<\/jats:sub>\u2009=\u20090.73\u2009\u00b1\u20090.05 and 1.13\u2009\u00b1\u20090.07\u2009\u00b5M, respectively, compared to novobiocin with an IC<jats:sub>50<\/jats:sub> value of 0.17\u2009\u00b1\u20090.02\u2009\u00b5M. The binding affinity and pattern of derivative <jats:bold>3e<\/jats:bold> toward the VEGFR\u20102 active site and compounds <jats:bold>3a<\/jats:bold>\u2013<jats:bold>c<\/jats:bold> and <jats:bold>3f<\/jats:bold> in the DNA gyrase active site were evaluated using molecular modeling. Overall, ADME studies of the synthesized coumarin derivatives displayed promising pharmacokinetic properties.<\/jats:p>","DOI":"10.1002\/ddr.22037","type":"journal-article","created":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T05:30:28Z","timestamp":1676266228000},"page":"475-499","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Coumarin derivatives with potential anticancer and antibacterial activity: Design, synthesis, VEGFR\u20102 and DNA gyrase inhibition, and in silico studies"],"prefix":"10.1002","volume":"84","author":[{"given":"Soha H.","family":"Emam","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy Cairo University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6785-6394","authenticated-orcid":false,"given":"Rasha A.","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy Cairo University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8472-9880","authenticated-orcid":false,"given":"Eman O.","family":"Osman","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy Cairo University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed I. 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