Chloramphenicol

Pongs, Olaf

doi:10.1007/978-3-642-46403-4_3

Cited by 33 publications

(33 citation statements)

References 71 publications

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“…The position of the CAM scaffold, through which the PA is linked, is of paramount importance; connection of PA to the 3-position of the 2-aminopropane-1,3-diol moiety of CAM, instead of the dichloroacetyl tail, leads to a strong reduction of potency as well as to an enhancement of the k off value (compare compounds 2 and 7 ). This is in agreement with previous studies indicating that the conformation and integrity of the 2-aminopropane-1,3-diol portion of CAM are both essential for the activity of the drug (22,45). The design of compound 7 was based on X-ray crystallographic observations in Deinococcus radiodurans 50S ribosomal subunit complexed with CAM (46), according to which the primary hydroxyl group of CAM interacts with the O 4 of U2506 ( E. coli numbering is used throughout the text), through a Mg 2+ ion that coordinates both groups.…”

Section: Discussionsupporting

confidence: 93%

Conjugation with polyamines enhances the antibacterial and anticancer activity of chloramphenicol

et al. 2014

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Chloramphenicol (CAM) is a broad-spectrum antibiotic, limited to occasional only use in developed countries because of its potential toxicity. To explore the influence of polyamines on the uptake and activity of CAM into cells, a series of polyamine–CAM conjugates were synthesized. Both polyamine architecture and the position of CAM-scaffold substitution were crucial in augmenting the antibacterial and anticancer potency of the synthesized conjugates. Compounds 4 and 5, prepared by replacement of dichloro-acetyl group of CAM with succinic acid attached to N4 and N1 positions of N8,N8-dibenzylspermidine, respectively, exhibited higher activity than CAM in inhibiting the puromycin reaction in a bacterial cell-free system. Kinetic and footprinting analysis revealed that whereas the CAM-scaffold preserved its role in competing with the binding of aminoacyl-tRNA 3′-terminus to ribosomal A-site, the polyamine-tail could interfere with the rotatory motion of aminoacyl-tRNA 3′-terminus toward the P-site. Compared to CAM, compounds 4 and 5 exhibited comparable or improved antibacterial activity, particularly against CAM-resistant strains. Compound 4 also possessed enhanced toxicity against human cancer cells, and lower toxicity against healthy human cells. Thus, the designed conjugates proved to be suitable tools in investigating the ribosomal catalytic center plasticity and some of them exhibited greater efficacy than CAM itself.

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Section: Discussionsupporting

confidence: 93%

Conjugation with polyamines enhances the antibacterial and anticancer activity of chloramphenicol

et al. 2014

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“…Due to its sites of interaction with the 50S subunit, Em is a competitor of Cm (23). We observed that addition of Em to ribosomes prior to peptide or simultaneously with the peptide partially reversed peptide inhibition of PT (Fig.…”

mentioning

confidence: 71%

Anti-peptidyl transferase leader peptides of attenuation-regulated chloramphenicol-resistance genes.

Harrod²,

Rogers³

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

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“…Much early work on the relationship between the structure of Cm and its antibiotic activity (summarized by Pongs, 1979) emphasized the importance of an unmodified primary alcohol at C-3Ј. Consistent with this, bacterial resistance to Cm is commonly mediated by enzymic acetylation of the C-3Ј hydroxyl group (Shaw and Leslie, 1991).…”

Section: Discussionmentioning

confidence: 91%

“…1 a broad-spectrum antibiotic that inhibits protein biosynthesis by binding reversibly to the peptidyl transferase center of 50 S ribosomal subunits (Pongs, 1979), is produced by Streptomyces venezuelae and some related species (Vining and Westlake, 1984). During growth under conditions where Cm is not produced, S. venezuelae is relatively sensitive to the antibiotic, but high-level resistance is induced by exposure to Cm; in cultures grown under Cmproducing conditions, resistance increases concurrently with Cm synthesis.…”

mentioning

confidence: 99%