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Recent advances in synthetic methodologies, including multicomponent 1,3\u2010dipolar cycloadditions, organocatalytic cascades, and one\u2010pot protocols, have facilitated the efficient synthesis of a wide variety of derivatives for SAR studies. A diverse range of classes, including pyrrolidine, cyclopropyl carboxamide, carbamate, oxadiazoline, pyrrolizidine, and furan derivatives, show cytotoxicity in the submicromolar\u2010to\u2010low micromolar range with good selectivity. The SAR studies suggest that substitution on the isatin core generally enhances biological activity in individual series, especially with electron\u2010withdrawing groups, but these effects are scaffold dependent. Furthermore, spirooxindole derivatives have been reported to show antibacterial activity, including TrpRS inhibition, antimicrobial, acetylcholinesterase inhibition, \u03b1\u2010glucosidase inhibition, antiviral, and anticonvulsant activities. The recent patents, especially on MDM2 inhibitors and other anticancer agents with nanomolar potency, provide further evidence for the continued interest in spirooxindole\u2010based drug discovery. This review highlights the recent advancements in spirooxindole chemistry involving synthetic strategies, SAR, biological activities, and recent patents.<\/jats:p>","DOI":"10.1002\/cmdc.70468","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T03:44:25Z","timestamp":1788234265000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spirooxindole Derivatives as Emerging Scaffolds in Drug Discovery: Synthetic Strategies, Structure\u2013Activity Relationship, and Biological Activities"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4196-0031","authenticated-orcid":false,"given":"Rakesh Chandra","family":"Kalita","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences Lovely Professional University  Phagwara Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarbanga","family":"Bezbaruah","sequence":"additional","affiliation":[{"name":"Royal School of Pharmacy The Assam Royal Global University  Guwahati Assam India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0127-2123","authenticated-orcid":false,"given":"Deepshikha","family":"Patle","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Lovely Professional University  Phagwara Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28020618"},{"key":"e_1_2_10_3_1","volume-title":"The IUPAC Compendium of Chemical Terminology","author":"2025, I. 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