P-47 Cryptophycins : 藍藻Nostoc sp.が生産する抗腫瘍性デブシベプチド(ポスター発表の部)

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In the course of screening over 1000 cyanobacteria for antitumor activity, we found that the lipophilic extract of Nostoc sp. GSV 224 showed strong cytotoxicity against KB (MIC 0.24ng/mL) and LoVo (MIC 6ng/mL). The extract also showed significant tumor-selective cytotoxicity in the Corbett assay. The MeOH extract of Nostoc sp. was separated by reversed-phase chromatography on ODS to afford cryptophycin A (1) as the major cytotoxic principle (KB IC_<50> 5pg/mL). This cyclic peptide had previously been isolated from Nostoc sp. ATCC 53789 as an antifungal agent, but its stereochemistry had not been determined. We determined the relative and absolute stereochemistry using a combination of chemical and spectral techniques including Marfey and modified Mosher methods. In the Corbett assay 1 was found to be strongly tumor selective and equally cytotoxic against drug-sensitive and drug-resistant tumor cells. Further HPLC (ODS) separation of the Nostoc sp. extract gave six minor cryptophycins B (2)-G (7). Their total structures were also determined. Interestingly cryptophycins are classified into two types; the major series possessing a monochlorinated L-O-methyltyrosine unit and the minor series possessing a D-O- methyltyrosine unit. Structure-activity relationship studies of cryptophycins and semisynthetic analogs were initiated. In preliminary in vivo assay 1 exhibited excellent activity against a broad spectrum of tumors implanted in mice.
天然有機化合物討論会の論文
1994-09-20

P-47 Cryptophycins : 藍藻Nostoc sp.が生産する抗腫瘍性デブシベプチド(ポスター発表の部)

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