Tropical protozoal diseases constitutes a group of endemic conditions that are mainly present in low-income countries of tropical and subtropical regions of Africa, Asia and America. They are caused by a variety of parasites, single-celled protozoa, which are transmitted to humans by insect vectors with complex life cycles. Major examples include malaria, Chagas disease, leishmaniasis and human African trypanosomiasis (HAT), which are caused by Plasmodium spp., T. cruzi, Leishmania spp. and T. brucei parasites, respectively. In general, tropical diseases caused by protozoa affect about 1 billion people worldwide, being responsible for great morbidity and mortality rates. The treatments remain a challenge as the existing therapies are outdated and present significant drawbacks in terms of a high degree of toxicity, cost, low therapeutic efficacy, low bioavailability, problematic administration treatment and parasite-resistance. Therefore, there is an urgent need to identify the lead structures for the rational design of safer and more potent antiprotozoal agents.

Historically, quinoline has been used a scaffold for the development of antimalarial agents with a well-defined mechanism based on the inhibition of polymerization of β-hematine and investigations are on-going for further optimization to improve the potency and elude resistance mechanisms. In recent decades, antimalarial drugs have been repurposed for the discovery of potential quinoline drugs against leishmaniasis. In particular, the 4-and 8-aminoquinolines represent a potential platform for the design of new leishmanicidal agents, acting through specific targets alteration of mitochondrial functions and immunostimulation of host-cells. Against Chagas Disease, the quinoline has emerged as an attractive platform to affect the parasite in the infected model. Meanwhile quinoline amides have been identified as a scaffold for further optimization against HAT. Other N-heterocycle analogues like quinazoline, pteridine, isoquinoline, quinoxaline and acridine form part of many of the most promising antiprotozoal agents. Despite the advances, further investigations are needed to elucidate the key role of the chemical functionalization in these N-heterocycles for the rational design of protozoal agents with drug-likeness properties and clinical perspectives. This Research Topic aims to seek novel approaches of identification of key pharmacophores for the design and development of new antiprotozoal agents based on quinoline and N-heterocyclic structures. The focus will be on Leishmaniasis, Malaria, Chagas Disease and HAT, but articles concerning other tropical diseases (i.e. toxoplasmosis, amoebiasis) caused by protozoa are also welcome.

We welcome Original Research, Review, Mini Review and Perspective articles on themes including, but not limited to:
• Synthesis and leishmanicidal activity of quinoline molecules
• Mechanistic and structure-activity relationship studies
• Computer-aided drug design
• Drug targets
• Immunological studies
• Drug repositioning
• New synthetic routes for preparation of aminoquinolines

Are you interested in contributing a manuscript to this Research Topic?

Quinoline and N-Heterocycle Analogues as Lead Structures for the Development of Antiprotozoal Agents