Total synthesis and cytotoxic activities of longamide B, longamide B methyl ester, hanishin, and their analogues.

Abstract

The marine alkaloids, longamide B (1), longamide B methyl ester (2), hanishin (3), and a series of non-naturally occurring analogues were synthesized in an efficient manner from inexpensive commercially available dl-aspartic acid dimethyl ester. The cytotoxicities of these natural products (1-3) and their analogues (9-15) were evaluated against human lung adenocarcinoma (A549) and human prostate cancer (PC3) cells. This is the first evaluation of the cytotoxicities of these alkaloids in these cancer cell lines and it revealed that analogue 15 had comparable cytotoxic activity to its natural parent compound, (±)-hanishin (3). This study provides useful information for further structural modification of these alkaloids in order to develop novel antitumor agents.

• Authors: Deng-Gao Zhao, Yan-Yan Ma, Wei Peng, Ai-Yu Zhou, Yu Zhang, Liugang Ding, Zhiyun Du, Kun Zhang
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 26 Issue 1 Pg. 6-8 (Jan 01 2016) ISSN: 1464-3405 [Electronic] England
• PMID: 26615890 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Pyrroles
• hanishin
• longamide B
• longamide B methyl ester

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Humans
• Molecular Structure
• Pyrroles (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship