Novel aminopeptidase N (APN/CD13) inhibitors derived from chloramphenicol amine

• Published in: Bioorganic & medicinal chemistry Vol. 19; no. 17; pp. 5190 - 5198
• Main Authors: Jia, Meirong, Yang, Kanghui, Fang, Hao, Xu, Yingying, Sun, Siwei, Su, Li, Xu, Wenfang
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01.09.2011; Elsevier
• Subjects: Amines - chemical synthesis; Amines - chemistry; Amines - toxicity; Aminopeptidase N inhibitors; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - toxicity; apoptosis; Binding Sites; Biological and medical sciences; CD13 Antigens - antagonists & inhibitors; CD13 Antigens - metabolism; chemistry; chloramphenicol; Chloramphenicol - chemistry; Chloramphenicol amine derivatives; Computer Simulation; Dipeptides - chemical synthesis; Dipeptides - chemistry; Dipeptides - toxicity; Drug Screening Assays, Antitumor; General aspects; Medical sciences; membrane alanyl aminopeptidase; metastasis; Pharmacology. Drug treatments; Propanolamines - chemical synthesis; Propanolamines - chemistry; Propanolamines - toxicity; Protease Inhibitors - chemical synthesis; Protease Inhibitors - chemistry; Protease Inhibitors - toxicity; QSAR; Structure-Activity Relationship; Synthesis; Synthesis; QSAR; Aminopeptidase N inhibitors; Chloramphenicol amine derivatives; Peptides; Leucine; Modeling; Structure activity relation; Molecular model; Chemical synthesis; Aminoalcohol; Enzyme; Aminopeptidases; Benzene derivatives; Prediction; Enzyme inhibitor; Inhibitor enzyme complex; Aniline derivatives; In vitro; Peptidases; Dipeptides; Hydrolases; Carboxamide; Aromatic amine; Membrane alanyl aminopeptidase
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2011.07.008

A series of compounds derived from (1S,2S)-2-amino-1-(4-nitrophenyl) propane-1,3-diol have been designed, synthesized as potential APN inhibitors. Aminopeptidase N (APN) is involved in different physiological and pathological processes of tumor cells, including proliferation, invasion, apoptosis and metastasis. Herein one series of compounds derived from commercially available (1S,2S)-2-amino-1-(4-nitrophenyl) propane-1,3-diol have been designed and synthesized. Furthermore, preliminary activity evaluation showed that some compounds elicited moderate inhibitory activity against APN with compounds 10e (IC50=6.1±0.5μM) possessing the best efficacy, which could be used as the lead compound in the future for anticancer agents research.