Antibiotics nucleoside analogues

An extensive database has demonstrated that many chemicals that are positive in this test also exhibit mutagenic activity in other tests. There are, however, examples of mutagenic substances, which are not detected by this test reasons for these shortcomings can be ascribed to the specific nature of the endpoint detected, differences in metabolic activation, or differences in bioavailability. On the other hand, factors which enhance the sensitivity of the bacterial reverse mutation test can lead to an overestimation of mutagenic activity. The bacterial reverse mutation test may not be appropriate for the evaluation of certain classes of chemicals for example, highly bactericidal compounds (e.g., certain antibiotics) and those which are thought (or known) to interfere specifically with the mammalian cell replication system (e.g., some topoisomerase inhibitors and some nucleoside analogues). In such cases, mammalian mutation tests may be more appropriate. 

The prototypical aminoacylated nucleoside analogue antibiotic is puromycin which inhibits the protein translation in all three domains of life. The chemical structure of puromycin is the same as that of tyrosylated adenosine, except for the presence of three added methyl groups and the replacement of an ester bond with an amide bond (Fig. 4.11). Puromycin mimics tyrosyl-tRNA so well that it binds to the A-site and gets incorporated into an elongating peptide. This leads to termination of translation because puromycin terminated peptides fall off the ribosome. Puromycin derivatives have been used crystallographically as peptidyl transferase substrates and have contributed to our understanding of the structure of the peptidyl transferase site (Fig. 4.5) [11, 16, 45],... 

Synthesis ofquinolone antibiotics The oxazolidinone antibiotics The synthesis of anti-viral nucleoside analogues The New Chiral Pool... 

The synthesis of cyclobut-A (113), a nucleoside analogue of the potent antiviral antibiotic oxetanocin, was accomplished using intramolecular [2 + 2] cycloaddition catalysed by Cu(I) ions.711 An inseparable mixture of four (E, Z, syn, anti) isomers of 114 was obtained in 70% chemical yield by irradiation of a triene 115 (Scheme 6.48). The nucleoside connection was then established via nucleophilic substitution of an acetate group by adenine and other transformations in several steps. 

Oxanosine (Fig. 8) was isolated as an antibiotic from Streptomyces (18). It is an unusual nucleoside analogue and shows weak antibacterial activity that is antagonized by guanine and guanosine. Oxanosine also has a weak antitumour effect on L1210 mouse leukemia. 

Natural products still have many surprises in store, as evidenced by the discovery of the antibiotic oxetanocin, a nucleoside analogue possessing a four-membered sugar ring other antibiotics apparently contain novel thio-sugar components. We have reviewed about 1460 references for this report. 

A brief review of nucleoside antibiotics has appeared which includes data on platenocidin, a new antibiotic from S. platensis" and another review covers nucleoside analogues exhibiting selective antiviral activity. ... 

Nucleoside Antibiotics Ribofuranosyl Analogues Oxetanocin and its Analogues Carbocyclic Nucleoside Analogues... 

---