Antitumor activity antibiotic

This was the first report of the successful screening of antibiotics for antitumor activity. Antibiotic research was thus expanded to also cover antitumor research. The term antitumor antibiotics was coined to include those compounds that are produced by microorganisms and inhibit the growth of tumor cells and tumors. Since that time, I have been continuing the study of new antitumor 2Uitlbiotics. Up to now with my collaborators I discovered eibout 65 antitumor antibiotics and elucidated structures of about 50 of them. Among them, bleomycin which we discovered in 1966 (76,79) has been used in the treatment of Hodgkin s lymphoma, tumors of the testis, and carcinomas of the skin, head, neck, and cervix. 

Antitumor activity - [ANTIBIOTICS - ANSAMACROLIDES] (Vol2) - [ANTIBIOTICS - ANSAMACROLIDES] (Vol2) -of enzymes [ENZYME APPLICATIONS - THERAPEUTIC] (Vol9) -ofhydantoins [HYDANTOIN AND ITS DERIVATIVES] (Vol 13)... 

Steroid Antibiotics. The steroid antibiotics are a stmcturaHy diverse class of steroids that have a common biological function, ie, antibacterial, antifungal, antiviral, or antitumor activities. This group of compounds can overlap with other steroid classes Hsted above. Eusidic acid [6990-06-3] (67), helvohc acid [29400-42-8] (68), and cephalosporin [13258-72-5] (69) exemplify a set of antibacterial steroids that contain a prolanostane skeleton with an... 

Oligosaccharides also occur widely as components (via glycosidic bonds) of antibiotics derived from various sources. Figure 7.20 shows the structures of a few representative carbohydrate-containing antibiotics. Some of these antibiotics also show antitumor activity. One of the most important of this type is bleomycin A2, which is used clinically against certain tumors. 

A number of mitomycin analogues have been prepared by precursor-directed biosynthesis [104]. A range of amines were fed to S. caespitosus, and novel derivatives of mitomycin C (type I analogues) and mitomycin B (type II analogues) were identified and in some cases (42-46 and 52-56 Scheme 11.4) isolated and characterized. Antibiotic and antitumor activities were comparable to those of mitomycin C, with the type I analogues more active than the type II analogues. 

The tightly bound chromophore could be extracted from the protein with methanol [186], and the major component of the extract was determined to have the enediyne structure 116 (Figure 11.21), related to chromophores of other chromoprotein antitumor agents such as neocarzinostatin. Additional minor components were extracted, variously containing an OH group instead of OMe attached to the enediyne core, with Cl instead of OMe when chloride was present in the buffer salt, or with OEt instead of OMe when ethanol was used for the extraction. Another byproduct was isolated in the form of structure 117, consistent with a facile cy-doaromatization reaction as observed for all other enediyne antibiotics. Surprisingly, 117 also displayed antibiotic and antitumor activity, perhaps due to alkylation of DNA or protein by the aziridine. The interpretation of these results was that 116 and the other enediyne byproducts were merely artifacts of the extraction procedure and that the true structure of the maduropeptin chromophore is the aziridine 118. 

Syntheses and antitumor activities of 7-0-(2,6-dideoxy-2-fluoro-o -L-ta-lopyranosyO-daunomycinone and -adriamycinone, T. Tsuchiya, Y. Ta-kagi, K. Ok, S. Umezawa, T. Takeuchi, N. Wako, and H. Umezawa, J. Antibiot., 39 (1986) 731-733. 

A new antitumor antibiotic, spergualin isolation and antitumor activity, T. Takeuchi, H. linuma, S. Kunimoto, T. Masuda, M. Ishizuka, M. Takeuchi, M. Hamada, H. Naganawa, S. Kondo, and H. Umezawa, J. Antibiot., 34(1981) 1619-1621. 

Quinone methides have been shown to be important intermediates in chemical synthesis,1 2 in lignin biosynthesis,3 and in the activity of antitumor and antibiotic agents.4 They react with many biologically relevant nucleophiles including alcohols,1 thiols,5-7 nucleic acids,8-10 proteins,6 11 and phosphodiesters.12 The reaction of nucleophiles with ortho- and /iara-quinone methides is pH dependent and can occur via either acid-catalyzed or uncatalyzed pathways.13-17 The electron transfer chemistry that is typical of the related quinones does not appear to play a role in the nucleophilic reactivity of QMs.18... 

Neooxazolomycin - polyene 261 metabolite with antibiotic and antitumor activity... 

Mizui Y, Sakai T, Iwata M, Uenaka T, Okamoto K, Shimizu H, Yamori T, Yoshimatsu K, Asada M. (2004) Pladienolides, new substances from culture of Streptomyces platensis Mer-11107. III. In vitro and in vivo antitumor activities. J Antibiot (Tokyo) 57 188-196. 

Konishi M, Sugawara K, Kofu F, Nishiyama Y, Tomita K, Miyaki T, Kawagushi H. (1986) Elsamicins, new antitumor antibiotics related to chartreusin. I. Production, isolation, characterization and antitumor activity. J Antibiot (Tokio) 39 784-791. 

Ueda, M., Manda, T., Matsumoto, S., Mukumoto, S., Nishigaki, F., Kawamura, 1. et al. (1994) FR901228, a novel antitumor bicydic depsipeptide produced by Chromobacterium violaceum No. 968. 111. Antitumor activities on experimental tumors in mice. Journal of Antibiotics (Tokyo), 47, 315-323. 

Baz, J. Canedo, L.M. Fernandez Puentes, J.L. (1997) Thiocoraline, a new depsipeptide with antitumor activity produced by a marine Micromonospora. J. Antibiot., 50, 738-41. 

The investigation of microorganisms has also resulted in the isolation of numerous indole derivatives with antibiotic and antitumor activity as well as substances primarily noteworthy for toxicity. One example is the mitomycin family, which has antitumor activity. Mitomycin... 

Awamycin and Ansathiazin. Awamycin and ansathiazin are produced by Streptomyces sp. No. 80-217 The structures for awamycin and ansathiazin were assigned on the basis of spectral data. Both antibiotics are active against gram-positive bacteria, and awamycin is reported to have antitumor activity. 

Mitomycin A, 1, is a natural product which shows potent antibiotic and antitumor activity, and has been the subject of extensive synthetic studies. French workers have described a simple procedure for one-pot preparation of the tricyclic skeleton of the mitomycins. Thus, simply mixing and stirring a solution of nitrosobenzene and (E,E)-hexa-2,4-dienal in absolute ethanol at... 

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