Synthesis and Biological Screening of Some Pyrazole Derivatives as Antimalarial and Antileishmanial Agents
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Date
2012-06
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Addis Ababa University
Abstract
Malaria and leishmania are very common parasitic diseases of the developing world and drug
resistance has hindered their efficient control. Pyrazole derivatives were synthesized using
aldol condensation and subsequent cyclization reactions. The compounds were synthesized in
a good yield (71.39%-95.23%). The compounds were purified by recrystallization and their
chemical structure was characterized by elemental microanalysis, IR, and 1HNMR
spectroscopy. In vivo antimalarial and in vitro antileishmanial activity was conducted using
four day suppression test and Alamar blue reduction method, respectively.
The results for antimalarial activity conducted using P. berghei infected mice at a dose level
of 48.46μmol/kg/day showed that all the synthesized compounds have lower activity than the
standard drug chloroquine phosphate. Compound IIc, 1-phenyl-4-(3-(thiophen-2-yl)-4,5-
dihydro-1H-pyrazol-5-yl)-3-p-tolyl-1H-pyrazole, showed relatively the highest %
suppression, 63.40%. The result for antileishmanial activity test revealed that all the
synthesized compounds except compound IIb had better antileishmanial activity than the
standard drug miltefosine (IC50= 3.1911 μg/ml). All of the synthesized compounds except
compounds III and IIIb exhibited lower antileishmanial activity compared to the standard
drug amphotericin B deoxycholate (IC50=0.0460 μg/ml). Compound IIIb, phenyl pyrazoline
with propanoyl side chain, 1-(3-phenyl-5-(1-phenyl-3-p-tolyl-1H-pyrazol-4-yl)-4,5-
dihydropyrazol-1-yl)propan-1-one, was found to be the most active (IC50= 0.0112) and two
hundred eighty five and four fold more active than the standards miltefosine and
amphotericin B deoxycholate, respectively.
Keywords: pyrazole, in vivo antimalarial activity, in vitro antileishmanial activity.
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Keywords
Pyrazole; In vivo antimalarial activity; In vitro antileishmanial activity