{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T12:28:43Z","timestamp":1786624123411,"version":"build-2736575974"},"reference-count":162,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Antimicrobial resistance is a major global health challenge that has created an urgent need for new antibacterial agents capable of overcoming emerging resistance mechanisms. Among nitrogen-containing heterocycles, pyrrolidine has been widely investigated in medicinal chemistry due to its structural versatility, favourable physicochemical properties, and ability to enhance interactions with biological targets. This review provides a comprehensive and critical overview of pyrrolidine-based compounds investigated for antibacterial applications. Relevant studies describing clinically approved antibiotics, natural products, synthetic derivatives, hybrid molecules, and antibacterial adjuvants containing a pyrrolidine scaffold were collected, classified, and critically evaluated, with particular emphasis on structural features, antibacterial activity, and structure\u2013activity relationships. The reviewed evidence demonstrates that the pyrrolidine moiety is present in several antibacterial drug classes, including carbapenems, cephalosporins, fluoroquinolones, lincosamides, streptogramins, and tetracyclines, where it contributes to improved target affinity, antibacterial potency, and pharmacokinetic behaviour. Numerous recently reported pyrrolidine derivatives have shown promising activity against clinically relevant, multidrug-resistant bacterial pathogens. The pyrrolidine scaffold is valuable for the design of next-generation antibacterial agents and resistance-modifying compounds, though further in vivo studies and pharmacological evaluation are required to support their clinical development.<\/jats:p>","DOI":"10.3390\/ijms27167225","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T11:33:46Z","timestamp":1786620826000},"page":"7225","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Role of Pyrrolidine in Antibacterial Drug Discovery: Clinically Approved Antibiotics, Novel Derivatives, and Future Perspectives"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4979-6903","authenticated-orcid":false,"given":"Aura","family":"Rusu","sequence":"first","affiliation":[{"name":"Pharmaceutical and Therapeutic Chemistry Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of T\u00e2rgu Mure\u0219, 540142 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioana-Maria","family":"Stroia","sequence":"additional","affiliation":[{"name":"Pharmaceutical and Therapeutic Chemistry Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of T\u00e2rgu Mure\u0219, 540142 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2564-9271","authenticated-orcid":false,"given":"Gabriel","family":"Hancu","sequence":"additional","affiliation":[{"name":"Pharmaceutical and Therapeutic Chemistry Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of T\u00e2rgu Mure\u0219, 540142 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5900-743X","authenticated-orcid":false,"given":"Corneliu","family":"Tanase","sequence":"additional","affiliation":[{"name":"Pharmaceutical Botany Department, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of T\u00e2rgu Mure\u0219, 540142 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3453-2243","authenticated-orcid":false,"given":"Livia","family":"Uncu","sequence":"additional","affiliation":[{"name":"Scientific Centre for Drug Research, Pharmaceutical and Toxicological Chemistry Department, \u201cNicolae Testemitanu\u201d State University of Medicine and Pharmacy, 165 Bd. 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