Pyrrolo(1,4)benzodiazepine antitumor antibiotics. Comparative aspects of anthramycin, tomaymycin and sibiromycin.

Hurley, Laurence H.

doi:10.7164/antibiotics.30.349

Cited by 171 publications

(91 citation statements)

References 41 publications

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“…This bioactivity has driven development of PBDs as antitumor agents (50). The structureactivity relationships of PBDs are well understood (51). Presence of the indole substituent on the PBD scaffold suggests that tilivalline will not form a similar covalent DNA adduct.…”

Section: Discussionmentioning

confidence: 99%

Enterotoxicity of a nonribosomal peptide causes antibiotic-associated colitis

Schneditz

Rentner

Roier

et al. 2014

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

108

181

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Antibiotic therapy disrupts the human intestinal microbiota. In some patients rapid overgrowth of the enteric bacterium Klebsiella oxytoca results in antibiotic-associated hemorrhagic colitis (AAHC). We isolated and identified a toxin produced by K. oxytoca as the pyrrolobenzodiazepine tilivalline and demonstrated its causative action in the pathogenesis of colitis in an animal model. Tilivalline induced apoptosis in cultured human cells in vitro and disrupted epithelial barrier function, consistent with the mucosal damage associated with colitis observed in human AAHC and the corresponding animal model. Our findings reveal the presence of pyrrolobenzodiazepines in the intestinal microbiota and provide a mechanism for colitis caused by a resident pathobiont. The data link pyrrolobenzodiazepines to human disease and identify tilivalline as a target for diagnosis and neutralizing strategies in prevention and treatment of colitis.bacteria | enteric microbiota | cytotoxin

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Section: Discussionmentioning

confidence: 99%

Enterotoxicity of a nonribosomal peptide causes antibiotic-associated colitis

Schneditz

Rentner

Roier

et al. 2014

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

108

181

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“…2). Transformation of tomaymycin to oxotomaymycin was proposed to be a resistance mechanism used by the cell (11). No clear candidate encoding the functionality for this transformation was identified in the characterized gene cluster, leaving open the possibility that this gene is located outside the gene cluster.…”

mentioning

confidence: 99%

Cloning and Characterization of the Biosynthetic Gene Cluster for Tomaymycin, an SJG-136 Monomeric Analog

Chou

Khullar

et al. 2009

Appl Environ Microbiol

140

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“…These results are consistent with the importance of the a-carbinol structure for antitumor activity documented with other antitumor antibiotics. 5,6,10) When safracins were given ip to mice implanted ip with P388 leukemia, intermittent (every 4th day on days 1, 5 and 9) or daily (days 1~5 and 1~9) treatments were more effective than a single dose on day 1 only for prolonging their life span. Accordingly, further studies on activity of safracins were made with these intermittent or daily dosage schedules.…”

Section: Discussionmentioning

confidence: 99%

Activity of safracins A and B, heterocyclic quinone antibiotics, on experimental tumors in mice.

Okumoto¹,

Kawana²,

Nakamura³

et al. 1985

J. Antibiot.

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Safracins A and B, new antibiotics produced by Pseudomonas fluorescens A2-2 , were tested for antitumor activity against mouse tumors . Structurally, these antibiotics belong to the saframycin family of antibiotics, and safracin B is 21-hydroxysafracin A . They showed antitumor activity against L1210 and P388 leukemias and B16 melanoma . The toxic and effective doses of safracin B were much lower than those of safracin A . Safracin B also prolonged the life span of tumor-bearing mice to a greater extent than safracin A . These results indicate that the a-carbinolamine structure plays an important role in the antitumor action of this type of antibiotic. Both safracins were, however, ineffective when their administration route differed from that used for inoculating tumor cells.

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Pyrrolo(1,4)benzodiazepine antitumor antibiotics. Comparative aspects of anthramycin, tomaymycin and sibiromycin.

Cited by 171 publications

References 41 publications

Enterotoxicity of a nonribosomal peptide causes antibiotic-associated colitis

Enterotoxicity of a nonribosomal peptide causes antibiotic-associated colitis

Cloning and Characterization of the Biosynthetic Gene Cluster for Tomaymycin, an SJG-136 Monomeric Analog

Activity of safracins A and B, heterocyclic quinone antibiotics, on experimental tumors in mice.

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