De Souza Marcus Vinícius Nora
FioCruz-Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos-Far Manguinhos, Rua Sizenando Nabuco, 100, Manguinhos, 21041-250 Rio de Janeiro-RJ.
ScientificWorldJournal. 2004 Jun 11;4:415-36. doi: 10.1100/tsw.2004.96.
(+)-discodermolide was isolated in 1990 by Gunasekera et al. from the deep-water Caribbean sponge Discodermia dissoluta. It attacks cancer cells in a similar way to the successful cancer drug Taxol that has become the best-selling anticancer drug in history. Taxol is also the first natural product described that stabilizes the microtubules involved in many aspects of cellular biology and that represent an important target of anticancer chemotherapeutics. However, (+)-discodermolide appears to be far more potent than Taxol against tumors that have developed multiple-drug resistance, with an IC50 in the low nanomolar range. Due to these excellent results, this natural product was licensed to Novartis Pharmaceutical Corporation in early 1998. The present review covers the history, biological activity, total synthesis, and synthetic analogs of (+)-discodermolide.
1990年,古纳塞克拉等人从加勒比海深水海绵溶盘海绵中分离出了(+)-盘状软骨素。它攻击癌细胞的方式与成功的抗癌药物紫杉醇相似,紫杉醇已成为历史上最畅销的抗癌药物。紫杉醇也是第一个被描述的天然产物,它能稳定参与细胞生物学许多方面的微管,而微管是抗癌化疗的一个重要靶点。然而,(+)-盘状软骨素对已产生多药耐药性的肿瘤的效力似乎比紫杉醇强得多,其半数抑制浓度(IC50)在低纳摩尔范围内。由于这些优异的结果,这种天然产物于1998年初被授权给诺华制药公司。本综述涵盖了(+)-盘状软骨素的历史、生物活性、全合成及合成类似物。