The protozoan diseases Human African Trypanosomiasis (HAT), Chagas disease (CD), and leishmaniases span worldwide and therefore their impact is a universal concern. The present regimen against kinetoplastid protozoan infections is poor and insufficient. Target-based design expands the horizon of drug design and development and offers novel chemical entities and potential drug candidates to the therapeutic arsenal against the aforementioned neglected diseases. In this review, we report the most promising targets of the main kinetoplastid parasites, as well as their corresponding inhibitors. This overview is part of the Special Issue, entitled “Advances of Medicinal Chemistry against Kinetoplastid Protozoa (Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp.) Infections: Drug Design, Synthesis and Pharmacology”.
The aim of the present investigation was to develop matrix tablet formulations for the in vitro controlled release of 2 new tuberculocidal adamantane aminoethers (compounds and), congeneric to the adamantane derivative , which is in final clinical trials, using carefully selected excipients, such as polyvinylpyrrolidone, sodium alginate and lactose. The tablets were prepared using the direct compression method and dissolution experiments were conducted using the US Pharmacopoeia type II apparatus (paddle method) in gastric and intestinal fluids. The results confirm that both analogues, albeit more lipophilic than, showed satisfactory in vitro release characteristics from solid pharmaceutical formulations. In conclusion, these formulations merit further assessment by conducting in the future bioavailability in vivo studies.
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.
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