Effect of Oral Treatment with Pyrazole Carbohydrazide Derivatives against Murine Infection by Leishmania amazonensis

Abstract

Newly synthesized pyrazole carbohydrazide derivatives with substituents X = Br/Y = NO(2) and X = NO(2)/Y = Cl were independently investigated in the CBA mouse model of cutaneous leishmaniasis. Animals were infected with Leishmania amazonensis and treated two weeks after the parasitic infection with the pyrazole carbohydrazides for 45 days. Oral treatment with both compounds controlled evolution of footpad cutaneous lesions and dissemination of parasites to draining lymph nodes. Nitric oxide generation was observed in supernatants of lymph node cells from infected CBA mice that were treated with these compounds. The pyrazole carbohydrazide derivatives did not show any toxicity or cause alterations in body weight, plasma concentrations of alanine aminotransferase and aspartate aminotransferase, and urinary creatinine levels, but promoted a small decrease in blood neutrophils. These results provide new perspectives on the development of drugs with activities against leishmaniasis.

Effectiveness of Novel 5‐(5‐amino‐1‐aryl‐1H‐pyrazol‐4‐yl)‐1H‐tetrazole Derivatives Against Promastigotes and Amastigotes of Leishmania amazonensis

“…However, a close examination of the similar compounds imidazole and tetrazole groups revealed that their leishmanicidal activity is strongly bound to the nature and position of the substituent on the phenyl group (Scheme ). Compound with no structural modification (R = H) compared with tetrazole ( 3a ), IC 50 = 388 ± 6.0 μ m (Table ), or imidazole rings, IC 50 = 365±3.5 μ m showed similar activity .…”

Pyrazole Carbohydrazide Derivatives of Pharmaceutical Interest

“…Apparently, the carbohydrazide moiety and the nature of the substituents introduced in the N -phenyl ring (R 1 and R 2 ) are crucial to determine the potentiality of the antimicrobial activity profile. A series of 1-(4- substituted -phenyl)-1 H -pyrazole-4-carboxylic acid (4- substituted -benzilidene)-hydrazide derivatives ( 19 ) marked leishmanicidal activity on L. amazonensis [30,31]. Another series of 1 H -pyrazole-4-carbohydrazides 20 presented moderate bactericidal and bacteriostatic properties [32].…”

4-(1H-Pyrazol-1-yl) Benzenesulfonamide Derivatives: Identifying New Active Antileishmanial Structures for Use against a Neglected Disease

“…is changing, with a tendency to urbanization and geographic expansion. Despite the high worldwide prevalence, few advances were made in the treatment of this disease [ 4 , 5 , 6 , 7 , 8 , 9 ]. There are no vaccines for Leishmaniasis and vector control is complex [ 2 , 8 ].…”

“…, with no toxicity to murine macrophages [ 11 ]. The literature also described that mice experimentally infected with L. amazonensis and treated with pyrazole carbohydrazide derivatives controlled the evolution of both footpads cutaneous lesions and dissemination of parasites to draining lymph nodes [ 6 ]. In addition the evaluation of pyrazole carboximidamide derivatives also revealed potential in vitro activity against L. amazonensis [ 12 ].…”

“…A therapy using an anti-inflammatory drug with antileishmanial properties, lower toxicity, cost, side effects and patient compliance may be very advantageous [ 6 ]. Previous reports from our laboratory described the in vitro and in vivo activity of pyrazoles against Leishmania parasites [ 6 , 11 , 12 , 13 ]. In this work we describe the synthesis of a new pyrazole family exploring this time the addition of a sulfonamide group.…”