Evaluation of some 1H-pyrazole derivatives as a dual acting antimalarial and anti-leishmanial agents
Pakistan Journal of Pharmaceutical Sciences
Department of Pharmaceutical Chemistry and Pharmacognosy, School of Pharmacy, Addis Ababa University, Addis Ababa, Ethiopia; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
The synthesis of a novel series of 1H-pyrazole derivatives was achieved by condensation of pyrazole aldehyde 1 with hydrazine hydrate to give hydrazone 7. On the other hand, cyclization of α,β-unsaturated ketone counterpart 2 using hydrazine hydrate in liquid aliphatic acids rendered compounds 4-6 and hydrazine hydrate in ethanol afforded compound 3. The later was allowed to react with aroyl chloride giving rise to compounds 8, 9. All compounds were tested for their in vivo anti-malarial and in vitro antileishmanial activities. The anti-malarial activity was performed using Plasmodium berghei infected mice, while the anti-leishmanial activity of the compounds was determined against Leishmania aethiopica promastigotes using alamar blue reduction assay. Compound 3, 1-(4-methylphenyl)-3-phenyl-4-[3-(2-thienyl)-2-pyrazolin-5-yl]-1H-pyrazole, possessed the highest anti-malarial activity with suppression of 70.26%. The highest anti-leishmanial activity was exhibited by compound 2, 1-(4-methylphenyl)-3-phenyl-4-[1-(2-thienyl)-prop-2-en-1-one]-1H-pyrazole, with an IC50 of 0.079μg/ml. Hydrazone 7 showed appreciable dual anti-malarial (suppression = 62.30%) and anti-leishmanial activity (IC50 = 1.823μg/ml). © 2014, Pakistan Journal of Pharmaceutical Sciences. All rights reserved.
1 (4 methylphenyl) 3 (phenyl) 1h pyrazole 4 carboxaldehyde hydrazone; 1 (4 methylphenyl) 3 phenyl 4 [1 (2 thienyl) prop 2 en 1 one] 1h pyrazole; 1 (4 methylphenyl) 3 phenyl 4 [1 propyl 3 (2 thienyl) 2 pyrazolin 5 yl] 1h pyrazole; 1 (4 methylphenyl) 3 phenyl 4 [3 (2 thienyl) 2 pyrazolin 5yl] 1h pyrazole; 1h pyrazole derivative; 4 [1 acetyl 3 (2 thienyl) 2 pyrazolin 5 yl] 1 (4 methylphenyl) 3 phenyl 1h pyrazole; 4 [1 aroyl 3 (2 thienyl) 2 pyrazolin 5 yl] 1 (4 methylphenyl) 3 phenyl 1h pyrazole; 4 [1 butyl 3 (2 thienyl) 2 pyrazoline 5 yl] 1 p methylphenyl 3 phenyl 1h pyrazole; alcohol; aliphatic carboxylic acid; antileishmanial agent; antimalarial agent; chloride; hydrazine; hydrazone derivative; ketone; pyrazole derivative; unclassified drug; antimalarial agent; pyrazole derivative; antimalarial activity; Article; controlled study; cyclization; drug design; drug effect; drug screening; drug synthesis; IC50; in vitro study; in vivo study; Leishmania; Leishmania aethiopica; male; mouse; nonhuman; Plasmodium berghei; promastigote; animal; drug effects; toxicity; Animals; Antimalarials; Leishmania; Male; Mice; Plasmodium berghei; Pyrazoles