Spirooxindole and Spirocyclic Scaffolds in Anticancer Drug Discovery: Design, Synthesis, Target Identification, and Preclinical Evaluation

Cancer is one of the leading causes of mortality worldwide, and current therapies face significant limitations in terms of drug resistance and systemic toxicity. The search for novel small molecules with selective antitumor activity has positioned heterocyclic scaffolds at the forefront of anticancer drug discovery. Among these, the spirooxindole motif has attracted sustained interest due to its structural resemblance to bioactive alkaloids, inherent molecular complexity, and broad synthetic accessibility. Compounds bearing the spirooxindole pharmacophore have shown potent activity against diverse cancer cell lines, acting through mechanisms that include apoptosis induction, cell cycle arrest, and inhibition of oncogenic signaling pathways. Parallel advances in stereoselective synthesis and in silico methods have accelerated the design and preclinical evaluation of optimized derivatives.Despite the promising pharmacological profile of spirooxindole derivatives, systematic characterization of their structure–activity relationships (SARs), mechanistic basis of action, and in vivo efficacy remains incomplete. The translational potential of these compounds is further constrained by limited data on selectivity across cancer types, stereochemical dependence of biological activity, and metabolic stability.This Research Topic aims to consolidate and advance knowledge in the field by bringing together original research, reviews, and mechanistic studies that address these gaps. It invites contributions spanning the full discovery pipeline, from rational scaffold design and enantioselective synthesis to biological screening against relevant cancer models, computational target identification, and early-stage pharmacokinetic evaluation. Special emphasis is placed on studies that elucidate the molecular targets and mechanisms underpinning anticancer activity, and on work that integrates computational approaches (docking, molecular dynamics, QSAR) with experimental methods to guide lead optimization. By assembling these perspectives, the collection aims to map the current landscape of spirooxindole pharmacology and identify clear directions for therapeutic development of related spirocyclic molecules as anticancer agents.This Research Topic welcomes original research articles, systematic and narrative reviews, mini-reviews, and perspective pieces. Contributions may address, but are not limited to:• Stereoselective and asymmetric synthesis of spirooxindole and related spirocyclic anticancer compounds, supported by experimental evaluation or in-depth discussion of their anticancer activity• Structure–activity relationship (SAR) and lead optimization studies grounded in experimental measures of biological activity• Molecular docking, molecular dynamics simulations, and QSAR analyses of spirooxindole derivatives, accompanied by experimental validation or a substantive discussion of the underlying anticancer activity• In vitro and in vivo anticancer efficacy studies against colorectal, breast, lung, and other solid tumors• Mechanisms of action: apoptosis, autophagy, cell cycle arrest, and signaling pathway modulation• Drug delivery and formulation strategies for spirooxindole-based compounds• Pharmacokinetic and metabolic profiling of novel derivativesSubmissions should demonstrate selectivity against cancer cell lines and, where applicable, provide comparative data against normal cell lines. Multidisciplinary studies combining computational design with experimental validation are particularly encouraged.All submissions must address the biological and pharmacological activity or mechanistic studies to support the bioactivity of the compounds studied. Purely synthetic or purely computational manuscripts fall outside the scope of this Research Topic. Topic editors: Satyanarayana Mavurapu, Dr. Pratap Chandra Acharya, Kenichiro Shimokawa, Divya Utreja Source: https://www.frontiersin.org/research-topics/82647/spirooxindole-and-spirocyclic-scaffolds-in-anticancer-drug-discovery-design-synthesis-target-identification-and-preclinical-evaluation