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The results exhibited that 13 compounds have from potent to good activity. Among those, five derivatives (<jats:bold>6<\/jats:bold>, <jats:bold>7<\/jats:bold>, <jats:bold>9<\/jats:bold>, <jats:bold>14a<\/jats:bold>, and <jats:bold>14b<\/jats:bold>) displayed the potent activities against the different isolates tested (MIC\u2009&lt;\u20090.25\u2009\u00b5g\/ml with bacteria and &lt;8\u2009\u00b5g\/ml with fungi) compared with Ciprofloxacin (CIP) and Fluconazole (FCA). Additionally, the potent adamantanes showed bactericidal and fungicidal effects based on (MBCs and MFCs) and the time\u2010kill assay. The most active adamantane derivatives <jats:bold>7<\/jats:bold> and <jats:bold>14b<\/jats:bold> exhibited a synergistic effect of \u03a3FIC\u2009\u2264\u20090.5 with CIP and FCA against the bacterial and fungal isolates. Moreover, no antagonistic effect appeared for the tested derivatives. Additionally, the interaction of DNA gyrase and topoisomerase IV enzymes with the compounds <jats:bold>6<\/jats:bold>, <jats:bold>7<\/jats:bold>, <jats:bold>9<\/jats:bold>, <jats:bold>14a<\/jats:bold>, and <jats:bold>14b<\/jats:bold> exhibited potent antimicrobial activity using in vitro biochemical assays and gel\u2010based DNA\u2010supercoiling inhibition method. The activity of DNA gyrase and topoisomerase IV enzymes showed inhibitory activity (IC<jats:sub>50<\/jats:sub>) of 6.20\u2009\u00b5M and 9.40\u2009\u00b5M with compound <jats:bold>7<\/jats:bold> and 10.14\u2009\u00b5M and 13.28\u2009\u00b5M with compound <jats:bold>14b<\/jats:bold>, respectively. Surprisingly, exposing compound <jats:bold>7<\/jats:bold> to gamma irradiation sterilized and increased its activity. Finally, the in\u2010silico analysis predicted that the most active derivatives had good drug\u2010likeness and safe properties. Besides, molecular docking and quantum chemical studies revealed several important interactions inside the active sites and showed the structural features necessary for activity.<\/jats:p>","DOI":"10.1002\/ddr.21960","type":"journal-article","created":{"date-parts":[[2022,6,18]],"date-time":"2022-06-18T08:14:51Z","timestamp":1655540091000},"page":"1305-1330","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["A new exploration toward\u00a0adamantane derivatives as potential anti\u2010MDR agents: Design, synthesis, antimicrobial, and radiosterilization activity as potential topoisomerase IV and DNA gyrase inhibitors"],"prefix":"10.1002","volume":"83","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8542-7465","authenticated-orcid":false,"given":"Ahmed","family":"Ragab","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Science (Boys) Al\u2010Azhar University  Nasr City Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1084-3904","authenticated-orcid":false,"given":"Moustafa S.","family":"Abusaif","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science (Boys) Al\u2010Azhar University  Nasr City Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1962-8629","authenticated-orcid":false,"given":"Dina S.","family":"Aboul\u2010Magd","sequence":"additional","affiliation":[{"name":"Drug Radiation Research Department, National Center for Radiation Research and Technology (NCRRT) Egyptian Atomic Energy Authority  Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed M. 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