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

Sherine Nabil Khattab; Nesreen Saied Haiba; Ahmed Mosaad Asal; Adnan A Bekhit; Aida A Guemei; Adel Amer; Ayman El-Faham

doi:10.1016/j.bmcl.2017.01.003

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

Bioorg Med Chem Lett. 2017 Feb 15;27(4):918-921. doi: 10.1016/j.bmcl.2017.01.003. Epub 2017 Jan 5.

Authors

Sherine Nabil Khattab¹, Nesreen Saied Haiba², Ahmed Mosaad Asal³, Adnan A Bekhit⁴, Aida A Guemei⁵, Adel Amer⁶, Ayman El-Faham⁷

Affiliations

¹ Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia, Alexandria 21321, Egypt. Electronic address: sh.n.khattab@gmail.com.
² Department of Physics and Chemistry, Faculty of Education, Alexandria University, Egypt. Electronic address: nesreensaied@yahoo.com.
³ Department of Physics and Chemistry, Faculty of Education, Alexandria University, Egypt.
⁴ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt. Electronic address: adnbekhit@pharmacy.alexu.edu.eg.
⁵ Department of Clinical Pharmacology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt. Electronic address: guemei_a@yahoo.com.
⁶ Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia, Alexandria 21321, Egypt; Department of Applied Chemistry, Faculty of Applied Science, Taibah University, Saudi Arabia. Electronic address: adel.amer@alex-sci.edu.eg.
⁷ Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia, Alexandria 21321, Egypt; Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia. Electronic address: aymanel_faham@hotmail.com.

PMID: 28087274
DOI: 10.1016/j.bmcl.2017.01.003

Abstract

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.

Keywords: Amino acid hydrazides; Antileishmanial activity; Quinazolinones.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acids / chemistry*
Amphotericin B / pharmacology
Antiprotozoal Agents / chemical synthesis
Antiprotozoal Agents / chemistry*
Antiprotozoal Agents / pharmacology
Deoxycholic Acid / pharmacology
Drug Combinations
Inhibitory Concentration 50
Isomerism
Leishmania / drug effects
Magnetic Resonance Spectroscopy
Molecular Conformation
Phosphorylcholine / analogs & derivatives
Phosphorylcholine / pharmacology
Quinazolines / chemical synthesis
Quinazolines / chemistry*
Quinazolines / pharmacology
Structure-Activity Relationship

Substances

Amino Acids
Antiprotozoal Agents
Drug Combinations
Quinazolines
Deoxycholic Acid
Phosphorylcholine
miltefosine
Amphotericin B
amphotericin B, deoxycholate drug combination