Study of antileishmanial activity of 2-aminobenzoyl amino acid hydrazides and their quinazoline derivatives

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• 作者：Sherine Nabil Khattab^a ; ^{sh.n.khattab@gmail.com} ; Nesreen Saied Haiba^b ; ^{nesreensaied@yahoo.com} ; Ahmed Mosaad Asal^b ; Adnan A. Bekhit^c ; ^{adnbekhit@pharmacy.alexu.edu.eg} ; Aida A. Guemei^d ; ^{guemei_a@yahoo.com} ; Adel Amer^a ; ^e ; ^{adel.amer@alex-sci.edu.eg} ; Ayman El-Faham^a ; ^f ; ^{aymanel_faham@hotmail.com}
• 关键词：Amino acid hydrazides ; Quinazolinones ; Antileishmanial activity
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2017
• 出版时间：15 February 2017
• 年：2017
• 卷：27
• 期：4
• 页码：918-921
• 全文大小：475 K
• 卷排序：27

文摘

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 = 0.051 μM) has the best activity, 154 folds more active than reference standard drug miltefosine (IC50 = 7.832 μM), and half fold the activity of amphotericin B (IC50 = 0.035 μM). In addition, this compound was safe and well tolerated by experimental animals orally up to 250 mg/kg and parenterally up to 100 mg/kg.