Leishmaniasis constitutes a group of neglected diseases present in tropical and subtropical regions mainly with low-incomes. It is caused by a variety of Leishmania species and subspecies and it represents the third most common parasitic disease worldwide. Leishmaniasis affects about 12 million people annually in 98 developing countries annually and climate change and migration have increased its impact in non-endemic regions. Its treatment is limited and there are only two approved drugs based on pentavalent antimonials (e.g. glucantime and pentostam) against their different forms. A second line of leishmanicidal agents including pentamidine, amphotericin B and miltefosine are frequently used when the first treatment option failed; however, all these drugs present several disadvantages in terms of toxicity, cost, low therapeutic efficacy, prolonged administration treatment times and parasite-resistance. Therefore, there is an urgent need to identify the lead structures for the rational design of leishmanicidal agents. In recent decades, antimalarial drugs have been used upon repurposing for the discovery of potential quinoline drugs against leishmaniasis. In particular, 4- and 8-aminoquinolines represent a potential platform for the design of new leishmanicidal agents and they act through some specific targets including: (i) alteration of respiratory complex III with apoptosis consequences; (ii) enhancement of glycolytic ATP synthesis via a sterol-dependent diffusion process; (iii) depolarization of mitochondrial succinate dehydrogenase, (iv) accumulation in lipid membranes of the parasite and, (v) immunostimulation of host-cells. Recent investigations have revealed that the presence of tertiary amines as basic group as well as lipophilic moiety (e.g. cyclohexyl, phenyl, alkyl chains) are pivotal issues for the generation of selective and potent leishmanicidal agents. Despite the understanding on the structural features of quinolones and identification of its biological influence, further investigations are needed to identify a lead structure based on quinoline.

This Research Topic seeks manuscripts dealing with novel approaches of identification of key pharmacophores for the design and development of new leishmanicidal agents based-on quinoline structure, either for models of Cutaneous or Visceral Leishmaniasis. Mechanistic experimental studies as well as theoretical modelling that provide a better understanding on structure-property relationship and targets 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
• Structure-activity relationship studies
• Computer-aided drug design
• Drug targets
• Immunological studies
• Drug repositioning
• New synthetic routes for preparation of aminoquinolines

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Frontiers in Chemistry

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