title: Study of antileishmanial activity of 2-aminobenzoyl amino acid hydrazides and their quinazoline derivatives.
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 IC50better 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.
authors.affiliation: Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia, Alexandria 21321, Egypt. Electronic address: sh.n.khattab@gmail.com.
authors.forename: Sherine Nabil
authors.initials: SN
authors.lastname: Khattab
authors.affiliation: Department of Physics and Chemistry, Faculty of Education, Alexandria University, Egypt. Electronic address: nesreensaied@yahoo.com.
authors.forename: Nesreen Saied
authors.initials: NS
authors.lastname: Haiba
authors.affiliation: Department of Physics and Chemistry, Faculty of Education, Alexandria University, Egypt.
authors.forename: Ahmed Mosaad
authors.initials: AM
authors.lastname: Asal
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt. Electronic address: adnbekhit@pharmacy.alexu.edu.eg.
authors.forename: Adnan A
authors.initials: AA
authors.lastname: Bekhit
authors.affiliation: Department of Clinical Pharmacology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt. Electronic address: guemei_a@yahoo.com.
authors.forename: Aida A
authors.initials: AA
authors.lastname: Guemei
authors.affiliation: 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.
authors.forename: Adel
authors.initials: A
authors.lastname: Amer
authors.affiliation: 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.
authors.forename: Ayman
authors.initials: A
authors.lastname: El-Faham
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000666:Amphotericin B / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D003840:Deoxycholic Acid / Q000494:pharmacology; D004338:Drug Combinations; D020128:Inhibitory Concentration 50; D007536:Isomerism; D007891:Leishmania / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000494:pharmacology; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D000981:Antiprotozoal Agents; D004338:Drug Combinations; D011799:Quinazolines; D003840:Deoxycholic Acid; D010767:Phosphorylcholine; C039128:miltefosine; D000666:Amphotericin B; C059765:amphotericin B, deoxycholate drug combination
keywords: Amino acid hydrazides; Antileishmanial activity; Quinazolinones