Themed collection Neglected Tropical Diseases

Guest editors Nahid Ali, Steven L. Cobb and Charles Mowbray introduce the themed collection on ‘Neglected tropical diseases’.

Important pharmacokinetic and -dynamic parameters for the drug discovery and development of new treatments for cutaneous leishmaniasis.

This review highlights the key roles of proteomic techniques in the study of Leishmania spp., Trypanosoma cruzi and Trypanosoma brucei parasites.

The review presents the discovery of new dengue inhibitors by a phenotype-based approach.

After a century since the first antimonial-based drugs were introduced to treat the disease, anti-schistosomiasis drug development is again at a bottleneck with only one drug, praziquantel, available for treatment purposes.

Ligand-based similarity screening of proprietary pharmaceutical company libraries enables rapid hit to lead investigation of a chemotype with anti-leishmania activity.

Water-soluble oxadiazole-based HKT inhibitor library, comprising a new class of compounds for control of Aedes aegypti dissemination, act as competitive HKT enzyme inhibitors, promoting accumulation of the toxic metabolite 3-hydroxykynurenine in insect organism.

P218 is a potent inhibitor of M. ulcerans DHFR (K_i 3.2 nM).

A series of benzene sulphonamides with good potency and selectivity against Leishmania spp. intracellular amastigotes was identified by high-throughput screening.

The development of a chemical series with oral efficacy against visceral leishmaniasis is described.

The antileishmanial activity of a variety of 3-nitro and 3-amino-isoxazoles against promastigote and amastigote stages of L. donovani is described.

Structure–property and structure–activity studies identify regions that positively modulate aqueous solubility; though maintaining potent anti-trypanosomal potency proves challenging.

L. infantum isolates from an outbreak of canine leishmaniasis were obtained. Drug sensitivity assays and infectivity studies show significant differences with reference strains.

Synergistic and antagonist drug interactions of drug combinations against Leishmania drug sensitive and resistant cell lines.

Potent T. brucei methionyl-tRNA synthetase inhibitors built on two novel short and rigid linker systems.

Hit anti-leishmanial saponin structures selected following primary and secondary screening.

A series of benzimidazole phenylacetamides were developed from a phenotypic hit as novel trypanosomacides for Chagas disease and human African trypanosomiasis.

A quantum chemistry guided optimisation (leading to piceatannol analogue 3t) with a good understanding of the catechol binding mode to the bimanganese cluster of arginase.

2-{2-[3-(1-Adamantyl)-4-fluorophenyl]thiazol-4-yl}ethan-1-amine (1a) and 2-{2-[4-(1-adamantyl)phenyl]thiazol-4-yl}ethan-1-amine (2a) exhibit activity against T. brucei in the range of IC₅₀ = 0.42 μM and IC₅₀ = 0.80 μM, respectively.