Synthetic Strategies Toward Next-Generation Anticancer Agents

Synthetic organic chemistry remains the engine of anticancer drug development. Most clinically used cytotoxic agents derive from structurally complex natural products whose assembly, modification and diversification depend directly on advances in synthetic methodology. Progress in the field has repeatedly followed progress at the bench: new catalytic transformations, stereocontrolled routes and late-stage functionalization strategies have each opened regions of chemical space that were previously out of reach. Substantial obstacles persist. Many promising scaffolds are difficult to prepare on scale, resist selective modification at the positions that govern activity, or lose potency through metabolic degradation. Improving tumor selectivity without compounding synthetic difficulty remains a central design problem. Addressing it requires chemists working on methodology, on molecular design and on conjugation strategies to engage with a shared set of questions.This Research Topic brings together work in which synthetic chemistry drives the design of anticancer agents. We seek contributions reporting new synthetic routes to biologically relevant scaffolds, methods for the selective modification of complex molecules, and design strategies that improve potency, selectivity or pharmacokinetic behavior. Studies applying organofluorine chemistry, bioisosteric replacement and stereochemical control to anticancer molecular design are particularly welcome, as are approaches to semisynthesis and late-stage functionalization that shorten access to analog series. We also welcome conjugate, linker and prodrug chemistry directed at tumor-selective delivery, where the synthetic problem is the limiting factor rather than the biological hypothesis. The collection aims to assemble a coherent view of how methodological advances translate into better anticancer molecules, and to make the synthetic challenges that remain clearly visible to the wider community.We welcome Original Research, Review, Mini Review and Perspective articles on themes including, but not limited to:• Synthetic methodology applied to anticancer scaffolds• Total synthesis and semisynthesis of bioactive natural products• Late-stage functionalization and diversification of analog series• Organofluorine chemistry and bioisosteric replacement• Stereocontrolled synthesis and the role of chirality in biological activity• Conjugate, linker and prodrug chemistry for tumor-selective delivery• Structure-activity relationships enabled by new synthetic accessContributions should place synthetic chemistry at the center of the study and make its relevance to anticancer molecular design explicit. Biological evaluation, pharmacological data or structure-activity relationship studies strengthen a submission, although these are not required where the synthetic contribution stands on its own. Formulation studies and nanomaterials-based delivery systems without a substantial synthetic component fall outside the scope of this collection, as does purely computational work. Computational studies are welcome when they are directly integrated with experimental synthesis.Topic Editor Zhendong Jin is the founder of InnoBioPharma, LLC. All other Topic Editors declare no competing interests with regard to the Research Topic subject. Topic editors: Iwao Ojima, Zhendong Jin Source: https://www.frontiersin.org/research-topics/85511/synthetic-strategies-toward-next-generation-anticancer-agents