Anti-tumor reagents

So far, not much literature on the biological activity of iminophosphor-anes has appeared. Compounds possessing triorganylphosphoranylidenea-mino structural elements such as mitomycin (41) have proved to be interesting anti-tumor reagents the cancerostatic activity seems to be localized in the aziridine units of 40 (Scheme 19) [87PS(30)845]. 

Liu HL, Chen Y, Cui GH, Zhou JF. 2005. Curcumin, a potent anti-tumor reagent, is a novel histone deacetylase inhibitor regulating B-NHL cell line Raji proliferation. Acta Pharmacol Sin 26 603-609. 

As described in Chapter III, morusin (3) has been found to be anti-tumor promoter in a two-stage carcinogenesis experiment with teleocidin. Considering the similarity of the structures between morusin (3) and artonin E (7), artonin E (7) was expected to be an anti-tumor promoter. Furthermore we found a novel photo-oxidative cyclization of artonin E (7) as follow photo-reaction of artonin E (7) in CHCI3 containing 4% ethanol solution with high-pressure mercury lamp produced artobiloxanthone (8) and cycloartobiloxanthone (9), and the treatment of artonin E (7) with radical reagent (2,2-diphenyl-1-picrylhydrazyl DPPH) resulted in the same products, Fig. (15), [84]. 

The DNA-damaging agent bleomycin arrests the cell cycle of Jurkat cells defective in the G1 checkpoint in the G2 phase, and microtubule-affecting colchicine arrests it in the M phase [40]. Boromycin showed no effect on the cell cycle status of Jurkat cells at least up to 340 nM but potentiated anti-tumor activity of bleomycin in SCID mice inoculated with Jurkat cells. These data suggest that boromycin disrupts the cell cycle at the G2 checkpoint of cancer cells selectively, leading to sensitization of cancer cells to anti-cancer reagents. 

Isoquinolines can be prepared by a Bischler-Napieralski reaction involving a tertiary formamide 1555, which reacts with the dehydration reagent triphosgene to form the anti-tumor active nitidine chloride 1557 [1184]. As regards the reaction mechanism, it can be suggested that the first step affords the same intermediate chloroformate 1556 as the isocyanide-generating process. Then, a Friedel-Crafts acylation-like attack of the iminium cation at the benzene moiety affords the isoquinoline nitidine chloride 1557 in 91% yield. 

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