Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 23, Issue 13, Pages 3526-3533Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2015.04.024
Keywords
Imidazole; Amino acids; Angiotensin Converting Enzyme; Cytotoxicity; Inhibitors
Funding
- CPC Division, CSIR-IICT, Hyderabad through 12th FYP project (ORIGIN) [CSC0108]
- Department of Biotechnology (DBT)
- CSIR
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A series of novel 2-butyl-4-chloro-1-methylimidazole derived peptidomimetics were designed, synthesized and evaluated for their Angiotensin Converting Enzyme (ACE) inhibitor activity. 2-Butyl-4-chloro-1-methylimidazole-5-carboxylic acid 2 obtained after oxidation of respective carboxaldehyde 1, was condensed with various amino acid methyl esters 3a-k to give imidazole-amino acid conjugates 4a-k in very good yields. Ester hydrolysis of 4a-k with aqueous LiOH gave the desired peptidomimetics 5a-k. Screening all the new compounds 4a-k and 5a-k using ACE inhibition assay, resulted five compounds 4i, 4k, 5e, 5h and 5i as potent ACE inhibitors with IC50 of 0.647, 0.531, 1.12, 0.657 and 0.100 mu M with minimal toxicity. Among them, 5i emerged as most active ACE inhibitor with greater potency than marketed drugs Lisinopril, Ramipril and relatively equipotent to Benazepril, Quinapril and Enalapril. (C) 2015 Elsevier Ltd. All rights reserved.
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