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This article reports the first synthesis, characterization, and antimicrobial evaluation of <jats:italic>S<\/jats:italic>\u2010oxide analogs of <jats:italic>N<\/jats:italic>\u2010aminoalkylated azaphenothiazines as antibacterials and antifungals. The optimized synthetic protocol enabled the production of the desired azaphenothiazine sulfoxides <jats:bold>12a\u2013e<\/jats:bold> and sulfonyls <jats:bold>14a\u2013e<\/jats:bold>, respectively. In addition to the x\u2010ray crystal structure of azaphenothiazine sulfoxide intermediate <jats:bold>10<\/jats:bold>, each target compound was characterized using spectroscopy techniques. All of these were investigated in vitro for antibacterial and antifungal activity against several strains of bacteria and fungi. Biological assays revealed selective antibacterial activity, with sulfoxides (<jats:bold>12a\u2013e<\/jats:bold>) exhibiting broad inhibition and sulfones (<jats:bold>14a\u2013e<\/jats:bold>) showing selectivity toward gram\u2010negative bacteria. Compound <jats:bold>12c<\/jats:bold> demonstrated fourfold higher potency against E<jats:italic>scherichia<\/jats:italic> coli than the reference drug. In antifungal studies, compound <jats:bold>14c<\/jats:bold> showed the highest activity (MIC 1.2\u00a0\u00b5g\/mL against C<jats:italic>andida<\/jats:italic> albicans). Our in silico evaluations utilized molecular dynamic (MD) and docking studies for active\u2010site binding simulations, revealing favorable drug\u2010like properties and pharmacokinetics. Finally, toxicology assays determined all synthesized analogs to be non\u2010toxic to kidney and hepatic tissues. This report highlights the newly described <jats:italic>S<\/jats:italic>\u2010oxide azaphenothiazine conjugates and their potential as potent antimicrobial agents.<\/jats:p>","DOI":"10.1002\/cbdv.202403338","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T21:09:15Z","timestamp":1741727355000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Azaphenothiazine Conjugates: A New Class of Antimicrobial Compounds"],"prefix":"10.1002","volume":"22","author":[{"given":"Khushbu","family":"Kushwaha","sequence":"first","affiliation":[{"name":"Department of Chemistry University of Delhi  Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devan","family":"Buchanan","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry Augusta University  Augusta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel","family":"Nkosi","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry Augusta University  Augusta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jatin","family":"Jangra","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering &amp; Technology, Indian Institute of Technology Banaras Hindu University  Varanasi Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajnish","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering &amp; Technology, Indian Institute of Technology Banaras Hindu University  Varanasi Uttar Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep Kumar","family":"Singh","sequence":"additional","affiliation":[{"name":"Jindal Global Business School O.P. 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