Recent developments in the clinical activity of topoisomerase-1 inhibitors

Haglof, Karen; Popa, E; Hochster, Howard S.

doi:10.1016/j.uct.2006.05.010

Cited by 13 publications

(10 citation statements)

References 198 publications

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“…These have been accepted as an important target in anticancer drug discovery. [111][112][113][114][115] There are several clinically important classes of antitumorals drugs like anthracycline (doxorubicin and daunorubicin), epipodophyllotoxin (etoposide and teniposide), mitoxanthrone, amonafide, topotecan, irinotecan, camptothecin and amsacrine classes that are considered topoisomerase (TOP) inhibitors. [116][117][118][119] About 50% of anticancer agents available target cancer via This journal is © The Royal Society of Chemistry 2017 inhibition of the topoisomerase mechanism.…”

Section: Imidazoles As Topoisomerase Inhibitorsmentioning

confidence: 99%

Imidazoles as potential anticancer agents

2017

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Cancer is a black spot on the face of humanity in this era of science and technology. Presently, several classes of anticancer drugs are available in the market, but issues such as toxicity, low efficacy and solubility have decreased the overall therapeutic indices. Thus, the search for new promising anticancer agents continues, and the battle against cancer is far from over. Imidazole is an aromatic diazole and alkaloid with anticancer properties. There is considerable interest among scientists in developing imidazoles as safe alternatives to anticancer chemotherapy. The present article describes the structural, chemical, and biological features of imidazoles. Several classes of imidazoles as anticancer agents based on their mode of action have been critically discussed. A careful observation has been made into pharmacologically active imidazoles with better or equal therapeutic effects compared to well-known imidazole-based anticancer drugs, which are available on the market. A brief discussion of the toxicities of imidazoles has been made. Finally, the current challenges and future perspectives of imidazole based anticancer drug development are conferred.

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Section: Imidazoles As Topoisomerase Inhibitorsmentioning

confidence: 99%

Imidazoles as potential anticancer agents

2017

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“…topotecan, irinotecan) at the interface of the enzyme-DNA complex to induce cell-death. Topo I is the only target of these alkaloid compounds (6,7). Clinical activity includes phase I-III studies for the indicated FDA approved agents for ovarian, colon, small-and non-small cell lung cancers.…”

Section: Introductionmentioning

confidence: 99%

“…Clinical activity includes phase I-III studies for the indicated FDA approved agents for ovarian, colon, small-and non-small cell lung cancers. Other topoisomerase I inhibitors are being tested in the clinic, in the treatment of pancreatic, breast and hematologic malignancies (6).…”

Section: Introductionmentioning

confidence: 99%

Topoisomerase I as a target of erlotinib and gefitinib: Efficacy of combined treatments with camptothecin

Peleg

Bobilev

Priel

2014

International Journal of Oncology

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Topoisomerases are essential nuclear enzymes that work to resolve topological problems that normally occur during DNA metabolism. Their involvement in crucial DNA associated-processes, such as replication, transcription and repair, mark them as a target of chemotherapeutic drugs such as camptothecins (CPTs). Therefore, finding other agents that may alter their activity is of great importance. Previous data showed that certain tyrosine kinase antagonists, tyrphostins, inhibit the catalytic activity of the cellular topoisomerase I (topo I). We examined the effect of clinically used tyrosine kinase inhibitors (TKIs), erlotinib and gefitinib, on topo I in breast and prostate cancer cells. While erlotinib and gefitinib inhibit cellular topo I in treated cells without affecting the levels of the enzyme protein, in vitro assays show that erlotinib, but not gefitinib, inhibits the DNA relaxation activity of purified topo I. Erlotinib was found to reduce the DNA-binding ability of topo I, however, the reduction in topo I activity in gefitinib-treated cells is probably due to post-translational modifications of the enzyme protein. A combined treatment of either erlotinib or gefitinib with CPT increased the effect of CPT on the activity of cellular topo I, which supports the increased anticancer effect observed in MCF7 cells. These results suggest that topo I is a novel target of erlotinib and a combination of TKIs with topo I inhibitors may be an effective treatment for breast cancer.

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“…However, the clinical application of 9-NC was largely hampered because of its poor solubility (lower than 5 g/ml in distilled water, 25 • C) and stability (Verschraegen et al, 1998), which led to low therapeutic efficacy and a number of side effects such as neutropenia, thrombocytopenia, and diarrhea owing to the conversion of 9-NC from active lactone form to the inactive carboxylate form under physiologic conditions (illustrated in Fig. 1) (Haglof et al, 2006).…”

Section: Introductionmentioning

confidence: 99%