Leishmaniasis drug discovery: recent progress and challenges in assay development

Antichagasic, Leishmanicidal, and Trichomonacidal Activity of 2‐Benzyl‐5‐nitroindazole‐Derived Amines

“…These IC 50 values were much higher than those found for amphotericin B( Ta ble 3), av ery effective but also toxic drug, whichi sa dditionally very costly in its liposomal formulation. [17,18] However,IC 50 values achieved by our tested compounds were on the same order as those described for two other reference drugs against promastigotes of L. amazonensis. In fact, for miltefosine, IC 50 values of 16.8 mm [45] and 3.4 mm [46] have been published, whereas for pentamidine, values of 29.9 mm (10.19 mgmL À1 ) [47] and 4.8 mm [48] have been recorded.…”

“…The aqueous layer was evaporated to dryness, and the residue was triturated with diethyl ether (20 mL) to afford the desired amines as the corresponding hydrochlorides, which were collected by filtration and air-dried. (18) [11] (0.98 g, 2.51 mmol) and the corresponding amine (MeNH 2 /EtOH [33 %, w/w]o rM e 2 NH/ EtOH [33 %, w/w]; 30 mL) was stirred at room temperature for 24 h and then evaporated to dryness. After addition of 10 %a q. K 2 CO 3 (100 mL), the resulting amine was extracted with CHCl 3 (4 50 mL) and the organic phase was dried (MgSO 4 )a nd evaporated to dryness.…”

“…[12][13][14][15][16] Leishmaniasis is ag roup of parasitic diseases caused by different protozoa specieso ft he genus Leishmania,w hich are transmitted through the bite of hematophagous sandflies. [17,18] These diseases are distributed throughout most of the world, especially in tropical and subtropical areas, appearingi n9 8 countries, many of whicha re developing regions. In humans, depending on the particular species of Leishmania involved, the disease has three main clinical forms:c utaneous, mucocutaneous,a nd visceral leishmaniasis, with the last form being the most severe and life-threatening.…”

“…Pentamidine, amphotericin B, miltefosine, and paromomycin are generally considered second-line antileishmanial drugs. [17,18] The above-mentioned imidazo-a nd triazolopyrimidine-derived proteasome inhibitors [6] and repurposed human kinases inhibitors [7] appear very promising in this field as well. However,i ti s also necessary to obtain new antileishmanial agentso fl ower cost, greater effectiveness, and with lower adverses ide effects.…”

Antitrypanosomatid Pharmacomodulation at Position 3 of the 8‐Nitroquinolin‐2(1H)‐one Scaffold Using Palladium‐Catalysed Cross‐Coupling Reactions

“…Among these drugs, miltefosine is the only orally available drug. These drugs are either expensive (e.g., liposomal amphotericin B), present severe side effects (e.g., the nephrotoxicity of amphotericin B, the teratogenicity of miltefosine) or show an increasing lack of efficacy due to the emergence of resistant parasites (antimony derivatives and miltefosine) . This global issue calls for the discovery of new antikinetoplastid molecules.…”