Spirooxindole: Privileged Scaffolds Inmodern Medicinalchemitry- Synthetic Strategie, Pharmacological Relevance, and Future Therapeutic Perspectives

ABTRACTSpirooxindole represent one of the most valuable and structurally privileged scaffolds in contemporary medicinalchemistry. Their rigid 3D- architecture, high sp3 character, and tunable stereochemistry enable precise molecularrecognition, making them ideal candidates for targeting protein-protein interactions, kinases, tubulin, microbialenzymes, and efflux transporters involved in multidrug resistance (MDR). This review provides a comprehensivesummary of the structural significance of spirooxindole, their natural products origins, and the evolution of theirsynthetic methodologies- including organocatalysis, transition-metal catalysis, multicomponent reactions,radical/photoredoxstrategie, and cycloaddition pathways. We further examine their diverse pharmacologicalactivities such as anticancer, antimicrobial, antiviral, antimalarial, and CNS-protective effects. A special emphasis isplaced on their role in overcoming MDR, particularly through P-glycoprotein (P-gp) inhibition exemplified bypotent derivatives such as OY-103-B. Despite their therapeutic potential, challenges remain in ADMET properties,metabolic stability, and enantioselective manufacturing. Finally, we highlight emerging frontiers, including theincorporation of spirooxindoles into PROTACs, conjugate-based delivery systems, and computationally guided drugdesign. Overall, spirooxindoles continue to serve asindispensable molecule platforms for next-generationtherapeutics.