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This replacement generated a potent antifungal agent with no antibacterial activity. Notably, use of a 1,2-diaminocyclohexane moiety, as a conformationally-restricted isostere for ethylenediamine, potentiated the antifungal activity in both the <jats:italic>cis<\/jats:italic> and <jats:italic>trans<\/jats:italic> forms of N-(5-(2-([1,1\u2019-biphenyl]-4-yl)-4-methylthiazol-5-yl)-1,3,4-oxadiazol-2-yl)cyclohexane-1,2-diamine (compounds <jats:bold>16<\/jats:bold> and <jats:bold>17<\/jats:bold>). Both compounds <jats:bold>16<\/jats:bold> and <jats:bold>17<\/jats:bold> were void of any antibacterial activity; nonetheless, they showed equipotent antifungal activity <jats:italic>in vitro<\/jats:italic> to that of the most potent approved antifungal agent, amphotericin B. The promising antifungal effects of compounds <jats:bold>16<\/jats:bold> and <jats:bold>17<\/jats:bold> were maintained when assessed against an additional panel of 26 yeast and mold clinical isolates, including the <jats:italic>Candida auris<\/jats:italic> and <jats:italic>C<\/jats:italic>. <jats:italic>krusei<\/jats:italic>. Furthermore, compound <jats:bold>17<\/jats:bold> showed superior activity to amphotericin B <jats:italic>in vitro<\/jats:italic> against <jats:italic>Candida glabrata<\/jats:italic> and <jats:italic>Cryptococcus gattii<\/jats:italic>. Additionally, neither compound inhibited the normal human microbiota, and both possessed excellent safety profiles and were 16 times more tolerable than amphotericin B.<\/jats:p>","DOI":"10.1371\/journal.pone.0258465","type":"journal-article","created":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T17:29:01Z","timestamp":1636046941000},"page":"e0258465","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Evaluation of bisphenylthiazoles as a promising class for combating multidrug-resistant fungal infections"],"prefix":"10.1371","volume":"16","author":[{"given":"Mohamed","family":"Hagras","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nader S.","family":"Abutaleb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0244-3457","authenticated-orcid":true,"given":"Ahmed 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