Azene, Addisu Asfaw (2012) Synthesis of some Novel 2-Pyrazolyl-4(3h)-Quinazolinone Derivatives with Potential Antimalarial and Antileishmanial Activities. Masters thesis, Addis Ababa University.
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Abstract
In this work, some derivatives of 2-pyrazolyl-4(3H)-quinazolinones have been synthesized by cyclization and condensation reactions. The synthesized compounds were obtained in a good yield (55.9-94%). The chemical structures of the final compounds were also verified by spectroscopic tools (IR, 1H NMR and elemental microanalyses). The in vivo anti-malarial activity of these compounds against P.berghei infected mice was found to be moderate at oral dose of 48.46 μmol/kg/day. This dose is equivalent to 25 mg/kg of chloroquine phosphate which causes 100% inhibition of the parasite. Among the synthesized compounds, 2-(3-(thiophen-2-yl)- 4,5-dihydro-1H-pyrazol-5-yl)-3-phenylquinazolin-4(3H)-one, Xa, showed better activity with percent suppression of 65.89. The synthesized compounds were also evaluated for their in vitro anti-leishmanial activity against L. donovani. Among the synthesized compounds, compound IXe (IC50=0.0121 μg/ml) was found to possess four fold the potency of amphotericine B (IC50=0.0460 μg/ml) while it was two hundred sixty four (264) times more potent than miltefosine (IC50=3.1911 μg/ml). Compound Xa (IC50=0.0211 μg/ml) was twice more potent than amphotericine B and this is the second most active compound as anti-leishmanial agent among the synthesized compounds. The synthesized compounds exhibited better inhibitory activity as indicated by their lower IC50 than miltefosine, except for compound XI. Compound XI showed the least activity which might be due to the presence of a phenyl group on the pyrazole N1. Furthermore, in the thiophen series cyclization of α,β-unsaturated compounds to the corresponding pyrazoline analogs led to improvement in activity while the phenyl series showed conflicting results.
| Item Type: | Thesis (Masters) |
|---|---|
| Uncontrolled Keywords: | 2-pyrazolyl-quinazolin-4(3H)-one, in vivo anti-malarial activity, in vitro antileishmanial activity and acute toxicity |
| Subjects: | R Medicine > RS Pharmacy and materia medica |
| Divisions: | Africana |
| Depositing User: | Vincent Mpoza |
| Date Deposited: | 27 Jun 2018 07:10 |
| Last Modified: | 27 Jun 2018 07:10 |
| URI: | http://thesisbank.jhia.ac.ke/id/eprint/5970 |
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