Synthesis and antileishmanial activity of new 1-aryl-1H-pyrazole-4-carboximidamides derivatives

Abstract

A quimioterapia para as leishmanioses, doenças causadas por protozoários do gênero Leishmania, ainda permanece ineficiente em diversos tratamentos. Portanto, existe a necessidade de pesquisa por novos fármacos. Nesse trabalho, foram sintetizados derivados 1-aril-1H-pirazol-4-carboximidamidas, avaliadas as atividades leishmanicida e os efeitos citotóxicos in vitro, e realizado um estudo de relação estrutura-atividade (REA) com a série de compostos. O composto 2 apresentou um perfil de atividade que pode ser melhorado através de estratégias de modificação molecular da química medicinal.Chemotherapy for leishmaniasis, diseases caused by protozoa of the genus Leishmania, remains inefficient in several treatments. So there is a need to search for new drugs. In this work, we have synthesized 1-aryl-1H-pyrazole-4-carboximidamides derivatives and evaluated antileishmanial activities in vitro, as well as cytotoxic effects. Structure-activity relationship (SAR) studies were carried out with all the compounds of the series. Compound 2 showed an activity profile that can be improved through medicinal chemistry strategies.

A Recent Update: Antimicrobial Agents Containing Pyrazole Nucleus

“…Recently, researcher's attention has been paid to heterocycles containing nitrogen atom, particularly pyrazoles and their derivatives [10]. They have been found to denote versatile biological activities such as monoamine oxidase inhibitor [11,12], antihepatotoxicity [13,14], antileishmanial [15][16][17], anti-inflammatory [18][19][20], antiproliferative [21], tissue non-specific alkaline phosphatase inhibitor [22], cyclin-dependent kinase inhibitor [23], anticancer [24][25][26][27], antimicrobial [28][29][30], and antioxidant [31][32][33]. Development of novel chemical structures of pyrazole derivatives is currently a trending topic due to their wonderful biological actions [34][35][36][37].…”

Screening of some pyrazole derivatives as promising antileishmanial agent

“…Leishmaniasis is a group of vector-borne diseases caused by species of the genus Leishmania, a compulsory intracellular parasite of the mammalian host cell (dos Santos et al, 2011;Luiz et al, 2012). Leishmania parasites exist in two forms: amastigote in the mammalian host and a flagellated promastigote in the insect vector (dos Santos et al, 2011).…”

“…Leishmania parasites exist in two forms: amastigote in the mammalian host and a flagellated promastigote in the insect vector (dos Santos et al, 2011). Clinical manifestation of leishmaniasis occur in four major forms in humans: (i) visceral, the most severe and life-threatening form; (ii) cutaneous, originating as nodules and ulcers that may persist for years; (iii) diffuse cutaneous leishmaniasis, which is a long-lasting disease due to a deficient cellular-mediated immune response; and (iv) mucocutaneous, causing permanent lesions in the mouth, nose or genital mucosa (dos et al, 2011;Luiz et al, 2012;Sa´nchez-Moreno et al, 2012). This life-threatening disease that affects about 12 million people worldwide with 1.5 million to 2 million new cases of cutaneous leishmaniasis (CL) and 500,000 new cases of visceral leishmaniasis (VL) each year is endemic in the tropical and sub-tropical regions (Desjeux, *Corresponding author.…”

“…The epidemiological pattern of Leishmania species is changing, with a tendency to urbanization and geographic expansion. Despite the high worldwide prevalence, no vaccine for Leishmaniasis and complex vector control, few advances were made in the treatment of this disease ((dos et al, 2011;Marra et al, 2012).…”

“…Chemotherapy for leishmaniasis is generally ineffective mainly due to the emergence of drug-resistant strains and toxicity of the therapeutic agents (Marra et al, 2012) The pentavalent antimonials compounds, such as sodium stibogluconate (pentostan) and meglumine antimoniate (glucantime) are widely used as primary therapy, but they induce toxic side effects together with drug resistance (dos et al, 2011;Braga et al, 2007).…”