重新审视孟加拉霉素：新结构与抗肿瘤研究

Bengamides revisited: new structures and antitumor studies.

作者信息

Thale Z, Kinder F R, Bair K W, Bontempo J, Czuchta A M, Versace R W, Phillips P E, Sanders M L, Wattanasin S, Crews P

机构信息

Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA.

出版信息

J Org Chem. 2001 Mar 9;66(5):1733-41. doi: 10.1021/jo001380+.

DOI:10.1021/jo001380+

PMID:11262120

Abstract

The structural chemistry and biological activity of the bengamide class of compounds have been further characterized. Extracts prepared from recollected Jaspis cf. coriacea from five sites in Fiji were pooled. Six new bengamides, M (7b), N (8a), O (8b), P (9a), Q (9b), and R (10), were identified, accompanied by the known bengamides A (1a), B (1b), E (3a), F (3b), Y (5), Z (6), L (7a), G (11a), H (11b), and I (12). The structures of the new compounds were determined from spectroscopic data, and some were additionally confirmed by semisynthesis. Cytotoxicity screening data were obtained from the NCI-DTP 60 cell screen for bengamides A, B, and P. Bengamides A and B were more potent than bengamide P, with average IC(50) values of 0.046, 0.011, and 2.70 FM, respectively. The in vitro antitumor activity against MDA-MB-435 human mammary carcinoma was also determined for natural bengamides A, B, E, F, P, M, O, and Z and for synthetic samples of B and O. The best activity was observed for the natural bengamides A (IC(50) = 1 nM) and O (IC(50) = 0.3 nM).

摘要

对苯甲酰胺类化合物的结构化学和生物活性进行了进一步表征。将从斐济五个地点重新采集的类似革质扁形海绵（Jaspis cf. coriacea）制备的提取物合并。鉴定出六种新的苯甲酰胺，即M（7b）、N（8a）、O（8b）、P（9a）、Q（9b）和R（10），同时还有已知的苯甲酰胺A（1a）、B（1b）、E（3a）、F（3b）、Y（5）、Z（6）、L（7a）、G（11a）、H（11b）和I（12）。通过光谱数据确定了新化合物的结构，其中一些还通过半合成得到进一步确认。从美国国立癌症研究所药物开发部（NCI-DTP）的60种细胞筛选中获得了苯甲酰胺A、B和P的细胞毒性筛选数据。苯甲酰胺A和B比苯甲酰胺P更具活性，平均IC50值分别为0.046、0.011和2.70纳摩尔。还测定了天然苯甲酰胺A、B、E、F、P、M、O和Z以及B和O的合成样品对MDA-MB-435人乳腺癌的体外抗肿瘤活性。天然苯甲酰胺A（IC50 = 1纳摩尔）和O（IC50 = 0.3纳摩尔）的活性最佳。