Discovery of new A- and B-type laxaphycins with synergistic anticancer activity.

Abstract

Two new cyclic lipopeptides termed laxaphycins B4 (1) and A2 (2) were discovered from a collection of the marine cyanobacterium Hormothamnion enteromorphoides, along with the known compound laxaphycin A. The planar structures were solved based on a combined interpretation of 1D and 2D NMR data and mass spectral data. The absolute configurations of the subunits were determined by chiral LC-MS analysis of the hydrolysates, advanced Marfey's analysis and 1D and 2D ROESY experiments. Consistent with similar findings on other laxaphycin A- and B-type peptides, laxaphycin B4 (1) showed antiproliferative effects against human colon cancer HCT116 cells with IC50 of 1.7 µM, while laxaphycins A and A2 (2) exhibited weak activities. The two major compounds isolated from the sample, laxaphycins A and B4, were shown to act synergistically to inhibit the growth of HCT116 colorectal cancer cells.

• Authors: Weijing Cai, Susan Matthew, Qi-Yin Chen, Valerie J Paul, Hendrik Luesch
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 26 Issue 9 Pg. 2310-2319 (05 15 2018) ISSN: 1464-3391 [Electronic] England
• PMID: 29606488 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Laxaphycin A
• Lipopeptides
• Peptides, Cyclic

Topics

• Antineoplastic Agents (chemistry, isolation & purification, pharmacology)
• Cyanobacteria (chemistry)
• Drug Discovery
• Drug Screening Assays, Antitumor
• Drug Synergism
• HCT116 Cells
• Humans
• Lipopeptides (chemistry, isolation & purification, pharmacology)
• Peptides, Cyclic (chemistry, isolation & purification, pharmacology)
• Stereoisomerism