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JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Study of antileishmanial activity of 2-aminobenzoyl amino acid hydrazides and their quinazoline derivatives.
Bioorganic & Medicinal Chemistry Letters 2017 Februrary 16
A new small library of 2-aminobenzoyl amino acid hydrazide derivatives and quinazolinones derivatives was synthesized and fully characterized by IR, NMR, and elemental analysis. The activity of the prepared compounds on the growth of Leishmania aethiopica promastigotes was evaluated. 2-Benzoyl amino acid hydrazide showed higher inhibitory effect than the quinazoline counterpart. The in vitro antipromastigote activity demonstrated that compounds 2a, 2b, 2f and 4a had IC50 better than standard drug miltefosine and comparable activity to amphotericin B deoxycholate, which indicates their high antileishmanial activity against Leishmania. aethiopica. Among the prepared compounds; 2-amino-N-(6-hydrazinyl-6-oxohexyl)benzamide 2f (IC50 =0.051μM) has the best activity, 154 folds more active than reference standard drug miltefosine (IC50 =7.832μM), and half fold the activity of amphotericin B (IC50 =0.035μM). In addition, this compound was safe and well tolerated by experimental animals orally up to 250mg/kg and parenterally up to 100mg/kg.
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