Recent advancements in heterocyclic compounds as innovative tools for the investigation and treatment of malaria.

Malaria is one of the deadliest infectious diseases causing a substantial burden for millions of people worldwide. Despite the significant efforts for disease prevention and treatment, eradication of malaria remains a distant goal owing to the emergence and spread of resistant parasitic strains insensitive to almost all approved antimalarials, including the artemisinin-combination therapies. This significant therapeutic challenge demands an urgent need for new therapeutic options. As frontline components of established antimalarial drugs, heterocyclic compounds represent privileged scaffolds in this field. Diverse heterocyclic derivatives have been extensively studied for their antimalarial properties, with some recently investigated as putative next-generation drugs. In addition, heterocyclic antimalarial drug-derived chemical probes have been recently used as tools to dissect the underlying mode of action of long-date therapies, furnishing key insights for the rational development of innovative therapeutic options. Consequently, harnessing heterocyclic compounds is of great interest to current and future antimalarial drug research.This Research Topic aims to establish a comprehensive, interdisciplinary platform for high-quality research focusing on the identification of heterocyclic compounds and exploring their therapeutic properties for malaria prevention and treatment. The primary objective of the Topic is to highlight the most recent advances in the design, synthesis, optimization, and development of innovative compounds with disparate heterocyclic scaffolds and demonstrated activity against Plasmodium species, including drug-resistant strains.We seek contributions detailing structure-activity relationship studies for heterocyclic compounds from synthetic, semi-synthetic, or natural origin, identified by established drug discovery strategies, including target-based and/or phenotype-based approaches, highlighted for their prominent in vitro antimalarial activity, favourable safety profile, significant pharmacokinetic properties, and outstanding efficacy in in vivo models. We especially welcome chemical biology studies aiding in the dissection of the complexity of parasite’s biology, enhancing the comprehension of drug resistance, and elucidating the molecular basis for compounds’ efficacy and safety through target protein profiling studies.This Research Topic welcomes Original Research, Reviews, and other article types relevant to antimalarial drug discovery harnessing heterocyclic compounds. The Topic is intended to provide an interdisciplinary platform linking medicinal chemistry, parasitology, chemical biology, and early drug discovery efforts. By fostering collaboration across different fields, the collection aims to provide key insights in the field alongside closing the gaps regarding still undermined questions, with the ultimate goal of accelerating the development of new antimalarial drugs. Topics of interest include the identification of repurposed or de novo synthetic, semi-synthetic, or natural compounds, establishment of structure-activity relationships, structural characterization, in vitro and in vivo antiplasmodial evaluation, resistance-focused studies, chemical biology studies, mechanism of action investigations, safety profiling, pharmacokinetic assessment, and preclinical evaluation of promising leads. Contributions using biophysical tools, metabolomics, computational approaches, or studies focusing on synergistic combinations are also encouraged. Topic editors: Francesco Saccoliti, Alessandro Giraudo Source: https://www.frontiersin.org/research-topics/85542/recent-advancements-in-heterocyclic-compounds-as-innovative-tools-for-the-investigation-and-treatment-of-malaria