Bonnard Isabelle, Rolland Marc, Salmon Jean-Marie, Debiton Eric, Barthomeuf Chantal, Banaigs Bernard
Laboratoire de Chimie des Biomolécules et de l'Environnement, Université de Perpignan Via Domitia, 66860 Perpignan, France.
J Med Chem. 2007 Mar 22;50(6):1266-79. doi: 10.1021/jm061307x. Epub 2007 Feb 27.
From a mixed assemblage of Lyngbya majuscula rich marine cyanobacteria, we isolated a series of cell growth inhibitory cyclic peptides. The structures of the two major components, laxaphycins A (1) and B (2), and of two minor peptides, laxaphycins B2 (3) and B3 (4), were determined by spectroscopic methods and degradative analysis. Absolute configurations of natural and nonproteinogenic amino acids were determined by a combination of hydrolysis, synthesis of noncommercial residues, chemical derivatization, and HPLC analysis. The organism producing the laxaphycins was identified as the cyanobacterium Anabaena torulosa. The antiproliferative activity of laxaphycins was investigated on a panel of solid and lymphoblastic cancer cells. Our results demonstrate that in contrast to laxaphycin A, laxaphycin B inhibits the proliferation of sensitive and resistant human cancer cell lines and that this activity is strongly increased in the presence of laxaphycin A. This effect appears to be due to an unusual biological synergism.
从富含巨大鞘丝藻的混合海洋蓝细菌中，我们分离出了一系列具有细胞生长抑制作用的环肽。通过光谱方法和降解分析确定了两种主要成分——松弛藻素A（1）和B（2）以及两种次要肽——松弛藻素B2（3）和B3（4）的结构。通过水解、非商业性残基的合成、化学衍生化和高效液相色谱分析相结合的方法确定了天然和非蛋白质氨基酸的绝对构型。产生松弛藻素的生物体被鉴定为念珠藻。在一组实体癌细胞和淋巴细胞癌细胞上研究了松弛藻素的抗增殖活性。我们的结果表明，与松弛藻素A相反，松弛藻素B能抑制敏感和耐药的人类癌细胞系的增殖，并且在存在松弛藻素A的情况下这种活性会显著增强。这种效应似乎是由于一种不寻常的生物协同作用。
