Antibiotics antitumour activity

It is a highly toxic antibiotic with antitumour activity isolated from Streptomyces caespitosus. 

The S3 unit is also to be found in compounds of natural origin [28, 32, 33]. A very simple one, isolated from an edible mushroom, exhibits both S2 and S3 moieties [34, 35]. 5-Methylthio-l,2,3-trithiane [28] is another example close to charatoxin, and the presence of an allylic trisulfide, and its role as a triggering device for their antitumour activity, in enediyne antibiotics [36,37], is truly astonishing. 

The antitumour action of the natural antibiotic bleomycin is thought to involve the aerobic degradation of DNA by the Fe2+-bleomycin complex. In order to probe the mechanism of antitumour action of bleomycin, the 4-ethylamido[5,(2 -thienyl)-2-thiophene] imidazole iron(II) complex was synthesized [129]. It was studied in non-aqueous solution using cyclic voltammetry and showed antitumour activity in vitro, its action causing cleavage of the double helical DNA. 

Finally, we should mention a series of synthetic approaches to L-pyrophosphino-tricine 144, a cyclic analogue of L-phosphinotricine, and its Ala-Ala peptide 145, a cyclic analogue of bialaphos (tripeptide of L-phosphinotricine produced in nature by Streptomyces hydroscopicus) [186], As the final step, the procedures comprised enzyme-catalysed hydrolysis and resolution of the racemic mixtures formed into optical antipodes by a-chymotripsin. Both 1,2-azaphospholane 144 and its tripeptide 145 exhibit antitumour activity. Moreover, tripeptide 145 displayed a greater bactericidal activity than the antibiotic bialaphos. 

Some natural products contain an aziridine ring, e.g. mitomycins (3 mitomycin C). This is responsible for the cytostatic and antitumour activity of these antibiotics. Many synthetic aziridines have been screened for their antitumour activity. Some have reached the clinic, especially as antileukaemic agents, e.g. 4 and 5. 

Nucleoside antibiotic. Prod, by certain aerobic bacteria in the presence of purine and Actinomadura sp. Shows antitumour activity. Needles (H2O). 

C11H13N5O4 279.255 Nucleoside antibiotic. Prod, by Strepto-myces hygroscopicus. Shows antibacterial and antitumour activity. 

Anthracycline antibiotic. Prod, by Strep-tomyces coeruleorubidus ATCC31276. Shows antitumour activity. Red needles. Sol. MeOH, DMSO, acids, CHCb poorly sol. H2O, hexane. 

C48H64O21 977.021 Belongs to Chromomycin family of antibiotics. Metab. of a Streptomyces sp. LA-7017 and Streptomyces atrooliva-ceus. Shows antitumour activity. Cryst. (Me2CO). Sol. EtOAc, CHCI3, MeOH poorly sol. hexano H2O. 

C17H23N7O5 405.413 Nucleoside-type antibiotic. Degradn. prod, of Blasticidin S by microbes such as Pseudomonas marginalis, Pseudomonas avails and Fusarium oxysporum. Possesses antitumour activity. Sol. H2O fairly sol. MeOH poorly sol. Mc2CO, hexane. 

Glycoside antibiotic, struct, not fully known. Isol. from Nocardioides sp. 1681J. Inhibitor of 5 -Nucleotidase. Also shows antitumour activity. Powder. Sol. H2O, DMSO poorly sol. MeOH, hexane. 

C41H50N2O10 730.853 Anthracycline antibiotic. Isol. from Streptomyces pluricolorescens. Antibiotic which inhibits the growth of gram-positive bacteria. Also shows antitumour activity. Orange-red cryst. (EtOAc). Sol. MeOH, C Hs, acids poorly sol. Et20, H2O, hexane. 

Nucleoside antibiotic. Isol. from Strepto-myces showdoensis. Exhibits antitumour activity. Leaflets (Me2CO/C6Hs). Sol. H2O, EtOH, Me2CO, dioxan, DMF, butanol, MeOH fairly sol. EtOAc, CHCI3 poorly sol. CeHe, hexane, Et20. Mp 160-161°. [a]g -1-49.9 (c, 1 in H2O). pAa 9.29 (H2O). 222 (e 12600) 272... 

These antibiotics, which show antitumour activity, strongly inhibit the synthesis of purines in liver extracts and cause the accumulation of the formyl derivative of A -glycylribosylamine 5-phosphate (LIX). Under normal conditions the latter reacts with glutamine and ATP, in the presence of a liver enzyme, to form the amidine LX. Buchanan has shown that azaserine (XXIX) and DON (XXX) inhibit this reaction specifically, by competing with glutamine for the enzyme sitei s. After combining with the enzyme the... 

CigHjsNO M 357.319 Isol. from an Aspergillus sylvanecii strain. Shows antibiotic, antifungal and antitumour activity. Unstable orange cryst. (Me2CO). Mp 58-59.5°. [a]i, -39.4° (CHCI3). 

The antitumour activity of antibiotics, which may act by strand breakage through radical production from a metal-centered redox reaction, will be summarized in Chapter 7. The examples summarized here show the feasibility of design and use of a DNA-binding ligand (ranging from very simple to a molecular weight of 600) to deliver a metal to DNA, where... 

The broth of Streptomyces refuineus has afforded the antibiotic anthramycin (XXVIIIa) with antitumour activity. The constitution of the compound was established by spectroscopic methods [I32J. It has been synthesised [133] from V-benzoyloxy-4-methyl-2-nitrobenzoyl-L-hydroxyproline methyl ester... 

Mycophenolic acid (Lla), an antibiotic produced by several species of Penicillia and first isolated seventy years ago [210, 211], has recently been shown to have useful antitumour activity. Its structure was established by chemical means [212], and has been confirmed by synthesis [213a]. Birch reduction of (Lila) followed by rearrangement afforded the diene (LIII), which gave (Lllb) on condensation with dimethyl acetylenedicarboxylate. Selective demethylation of (Lllb) followed by cyclisation furnished the anhydride (Lib). Reduction of the anhydride ring to a y-lactone ring and... 

Aureolic acid, an antibiotic with antitumour activity isolated from a Strepto-myces species, has been shown to be identical with mithramycin [368, 369]. Acid hydrolysis of the compound has afforded [370] the aglycone chromo-mycinone (LXXVIIIb) and the sugars mycarose (LXXIXa), chromose C (LXXIXd), and oliose (LXXIXb). The points of attachment and sequence of the sugar chains, and the chirality of aureolic acid (LXXVIIIc) have been... 

Efficient syntheses of angustamycin A (458) (Scheme 89), a nucleoside antibiotic exhibiting modest antimicrobial and antitumour activities, and some base analogues of angustamycin A have been described. Reduction of the unsaturated keto-nucleosides (459) and (460) with sodium borohydride has provided... 

The highly active antitumour antibiotic CC-1065, molecule of which contains pyrroloindole fragment, was isolated in 1987 from Streptomyces zebensis. Its antitumour activity is many times greater than that of other known preparations [4]. This stimulated further development of synthetic methods for the preparation of pyrroloindoles. 

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