Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our studies in human epidermal keratinocytes as a model system have suggested that the antibiotic topoisomerase II inhibitors, novobiocin and nalidixic acid, may be of value for the treatment of hyperproliferative skin disorders. We have therefore conducted a pilot study of the clinical efficacy of these compounds for the treatment of psoriasis. The compounds were administered topically to psoriatic plaques in seven healthy patients over a period of 6 weeks. Nalidixic acid (2%) or novobiocin (2% or 5%) in methylcellulose were applied twice daily under occlusion, and methylcellulose alone was used as a control. In six of the seven patients, one or both compounds effected somewhat greater improvement than in the control within 3 weeks of treatment.
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PMID:Topical treatment of psoriasis with the topoisomerase inhibitors novobiocin and nalidixic acid: a pilot study. 303 23

Bimolane is a member of the bis(2,6-dioxopiperazine) class of drugs and has been widely used in China as an anti-neoplastic agent and for the treatment of psoriasis. Recent case reports indicate that bimolane is leukemogenic and is thought to exert its effects through the inhibition of topoisomerase II. However, there are no data showing the inhibition of topoisomerase II by this agent. In this report bimolane was shown to inhibit the activity of human topoisomerase II in vitro at concentrations of 100 microM and higher when pBR322 was used as the DNA substrate, whereas inhibition was seen at 1.5 mM when using kDNA as a substrate. The results of enzyme and DNA titration assays indicate that inhibition of topoisomerase II by bimolane occurred through interactions with DNA, similar to the mechanism seen with the epipodophyllotoxin-type inhibitors. These results provide evidence that bimolane is an inhibitor of topoisomerase II in vitro.
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PMID:Bimolane: in vitro inhibitor of human topoisomerase II. 946 Oct 29

ICRF-154 and bimolane have been used for the treatment of cancer, psoriasis, and uveitis in humans. Previous reports have revealed that the two drugs are topoisomerase II catalytic inhibitors, and patients treated with these agents have developed unique types of secondary leukemia. A study published in 1984 by Camerman and colleagues proposed that the therapeutic effects of bimolane could be due to ICRF-154, an impurity present within the bimolane samples that may also be responsible for the toxic effects attributed to bimolane. To date, this hypothesis has not been evaluated. In addition, little is known about the potential cytotoxic and genotoxic effects of ICRF-154. In this study, a combination of in vitro tests in human TK6 lymphoblastoid cells has been used to characterize the cytotoxic and genotoxic effects of ICRF-154 and bimolane as well as to compare the results for the two chemicals. ICRF-154 and bimolane were both cytotoxic, exhibiting very similar effects in three measures of cytotoxicity and cell proliferation. In the cytokinesis-block micronucleus assay with CREST-antibody staining, the two agents similarly induced chromosome breakage and, to a lesser extent, chromosome loss. Intriguingly, both drugs resulted in the formation of binucleated cells, perhaps as a consequence of an interference with cytokinesis. To further investigate their aneugenic effects, flow cytometry and fluorescence in situ hybridization analyses revealed that both compounds also produced similar levels of non-disjunction and polyploidy. In each of the cellular and cytogenetic assays employed, the responses of the ICRF-154-treated cells were very similar to those observed with the bimolane, and generally occurred at equimolar test concentrations. Our results, combined with those from previous studies, strongly suggest that bimolane degrades to ICRF-154, and that ICRF-154 is most likely the chemical species responsible for the cytotoxic, genotoxic, and leukemogenic effects exerted by bimolane.
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PMID:A comparative study of the cytotoxic and genotoxic effects of ICRF-154 and bimolane, two catalytic inhibitors of topoisomerase II. 2300 Apr 30