Novel Small Molecules, Plant Secondary Metabolites and Drug Delivery Strategies for Malaria Therapy

Malaria remains a major global health burden, and the continued emergence of resistance to frontline therapies, including artemisinin-based combination treatments, underscores the urgent need for new antimalarial agents and improved delivery strategies. Natural products, particularly secondary metabolites from plants and marine organisms, together with their synthetic derivatives and other small molecules, represent an important reservoir of promising antiplasmodial leads. However, many of these compounds fail to progress because of poor solubility, limited bioavailability, unfavorable pharmacokinetics, and other physicochemical challenges. Overcoming these barriers requires an integrated approach that combines medicinal chemistry, rational structural modification of bioactive scaffolds, and advanced pharmaceutical delivery systems. Lipid-based formulations, nanocarriers, and related technologies offer important opportunities to enhance stability, absorption, and therapeutic performance. This special issue will bring together research on antimalarial small molecules, natural-product-derived compounds, pharmacological evaluation, and innovative drug delivery approaches that can support translation from discovery to therapeutic application. The primary goal of this Research Topic is to address a critical bottleneck in antimalarial drug development: the disconnect between the discovery of bioactive small molecules and their successful translation into effective therapies. While numerous compounds—including synthetic molecules and secondary metabolites from plant and marine sources—demonstrate promising antiplasmodial activity, many fail due to poor physicochemical properties, limited bioavailability, and suboptimal pharmacokinetics. This Research Topic seeks to bridge this gap by promoting an integrated approach that combines medicinal chemistry, rational modification of bioactive scaffolds, and advanced drug delivery strategies. By bringing together interdisciplinary contributions spanning small-molecule design, natural product optimization, formulation science, and preclinical evaluation, the collection aims to highlight innovative solutions that enhance drug performance. Ultimately, this effort seeks to accelerate the progression of promising antimalarial candidates from early discovery toward clinically relevant therapeutic interventions.ScopeThis Research Topic invites contributions that explore innovative approaches to antimalarial drug discovery, with particular emphasis on the integration of small-molecule design and advanced drug delivery strategies. Areas of interest include the design and synthesis of novel antiplasmodial compounds; synthetic modification of secondary metabolites from plant and marine sources; structure–activity relationship studies; identification and validation of new drug targets; and pharmacological evaluation in relevant models. Contributions focusing on formulation approaches—such as lipid-based systems, nanocarriers, and bioavailability-enhancing technologies—are especially encouraged. Studies addressing physicochemical optimization, pharmacokinetics, and translational aspects of drug development are also within scope. We welcome Original Research Articles, Reviews, Mini-Reviews, and Methods papers that provide interdisciplinary insights and contribute to advancing effective and translatable antimalarial therapies. Topic editors: Julius Adesanwo, Olatomide Ayodeji Fadare, Eric Beitz Source: https://www.frontiersin.org/research-topics/79545/novel-small-molecules-plant-secondary-metabolites-and-drug-delivery-strategies-for-malaria-therapy