Tumor-inhibitory activity

Leo Paquette of Ohio State recently reported (J. Am. Chem. Soc. 125 1567, 2003) the total synthesis of jatrophatrione 1 and citlalitrione 2. These diterpenes, which share a central highly-subsituted 5-9-5 core, show remarkable tumor-inhibitory activity. 

Several factors are involved in the wide variation in tumor inhibitory activity of asparaginases from different sources (98). One obvious possibility is the rate of clearance of the enzyme from the circulation of the host animal, and Broome (26) was the first to obtain evidence implicating half-life as a factor in antitumor effectiveness. Guinea pig serum asparaginase, for example, has a half-life time of 11-19 hr, while a partially purified yeast asparaginase preparation without antilymphoma activity is almost completely cleared within 30 min. Differences in half-life alone cannot explain the differences in antitumor activity in all cases, however and the question still remains as to what structural features are responsible for rapid or slow clearance. Mashburn and Landin (85) have suggested that differences in half-life time may be related to the isoelectric point of the enzyme, and evidence also exists to support the idea that the tumor inhibitory activity of some asparaginases is related to their K, values (59, 67). 

Unfortunately 1-ASP was difficult to obtain from guinea pig serum in suffi-cient amounts. Thus, other potential sources for the enzyme had to be found, Mashbum and Wriston [12] successfully purified L coli 1-ASP and demonstrated its tumor-inhibitory activity, which opened the way for large-scale production of the enzyme. 

Crotepoxide, for example, was isolated from fruits of Croton macrostachys and has been shown to have significant tumor-inhibitory activity for Lewis lung carcinoma in mice (LL) and Walker intramuscular carcinosarcoma in rats (WM). 

The tumor-inhibitory activity of analogues of purine and pyrimidine bases led Shealy and several coworkers to synthesize a series of analogues of the imidazoles in the biosynthetic pathway to purine ribonucleotides and to test these analogues for antineoplastic effects. 59 Beginning... 

The c-DDP is attached to a preformed, water-soluble polymer, polybis(methyl-aminojphosphazene, I, that bears coordination sites on both the side-group and chain nitrogen atoms ". Compound I reacts with K2[PtCl4] in organic media with 18-crown-6-ether yielding a coordination complex, II, containing c-DDP which shows tumor inhibitory activity . 

Taxodione (180), a tumor-inhibitory diterpenoid quinone [70] has been the subject of synthetic endeavours [71] because of its unique structure as a quinone-methide and partly because of its tumor-inhibitory activity. Banerjee and Carrasco [72] developed an alternative synthesis of the ketone (179) whose transformation to taxodione (180) has already been accomplished by Matsumoto [73]. The synthetic route for the synthesis of the ketone (179) is described in "Fig (15)". 

Maytansine (218) was the first ansa macrolide shown to contain a 19-membered lactam ring with carbinolamine, epoxide, or aryl halide functions and appears to be the first member of the series reported to show significant in vivo tumor inhibitory activity [116]. 

Aristolochic acid-I exhibits tumor inhibitory activity against the adenocarcinoma 755 test system. Subsequently, however, when tested on mice, it was found to produce papillomas. Aristolochic acid-I is the probable causative agent in Balkan endemic nephropathy. A convenient fluorometric assay for its determination is based on hydrosulfite reduction to the lactam, and measurement of the intensity of fluorescence. ... 

Mice (a) Tumor inhibitory activity of black pepper in mice implanted with Ehrlich ascites tumor [68]... 

Resibufagenine (47), with no 140-hydroxy group, showed cardiotonic effects in hypotensive dogs. The tumor inhibitory activities of the dlhydro-bufadlenolldes withaferln A, wlthacnlstin, and the bufadienollde, ballebrigenln-3,5-dlacetate 3 were reported. 

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