国际药学与生命科学研究与发展杂志

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SYNTHESIS AND IN- VIVO PHARMACOLOGICAL EVALUATION OF SOME NOVEL 4(3H)- QUINAZOLINONE DERIVATIVES AS POTENTIAL ANTI-MALARIAL AGENTS

Mohammed Hussen Bule, Ariaya Haymete2, Belayneh kefale

In this work six 3-aryl-2-(substitutedstyryl)-4(3H)-quinazolinones derivatives were synthesized by the reaction of 3-aryl-2-methyl-4(3H)-quinazolinone (intermediate products) with different substituted aromatic aldehydes. Three intermediate products were synthesized by reacting 2-methyl-3, 1-benzoxazin-4-one, which was initially prepared by cyclizing anthranilic acid using acetic anhydride, with three aromatic amines. Their structures were confirmed using IR, 1HNMR, 13CNMR spectroscopic methods and elemental microanalyses. The synthesized compounds were evaluated for their in vivo antimalarial activity against P. berghei. Four of the synthesized compounds (IIIc, IVa, IVb and IVf) exhibited activity against the parasite. Among these compound IVa was found to be the most active compound. Results of acute toxicity study showed that oral administration of the synthesized compounds in single doses (100, 250 and 500mg/kg) had no adverse effects, indicating that the compounds have high safety margin and their LD50 is higher than 500 mg/kg. In general this study indicates that 4(3H)-quinazolinones derivatives are potential sources of lead compounds for antimalarial drugs.