Topoisomerase 1 and

Scheme 6 Structure of coralyne derivatives and a substituent in 8-position tested for cytotoxicity and topoisomerase 1 and II poisons...

Quantitative Structure-Activity Relationships of Heterocyclic Topoisomerase 1 and 11 Inhibitors... 

Fig. 6. DNA topoisomerases and DNA topology in eubacteria and eukaryotes. Upper panel DNA topoisomerases of the two domains the arrows with the same shading correspond to homologous DNA topoisomerases, 1 and 2 are for type I and type II DNA topoisomerases, respectively. Lower panel origin of negative supetcoiling in eukaryotes and eubacteria (see the text). JV > 0, positive supercoiling JV < 0, negative supercoiling.

The effects on fertility of inhibitors of topoisomerases 1 and 11 have not yet been fully elucidated. However, ovarian failure, amenorrhea, anovulatory cycles, and hypome-norrhea have been described in women receiving etoposide (150). 

Etievant C, Kruczynski A, Barret JM, Perrin D, van Hille B, Guminski Y, Hill BT. F 11782, a dual inhibitor of topoisomerases 1 and II with an original mechanism of action in vitro, and markedly superior in vivo antitumour activity, relative to three other dual topoisomerase inhibitors, intoplicin, aclarubicin and TAS-103. Cancer Chemother Pharmacol 2000 46(2) 101-13. 

The basic structure of camptothecin. Analogues of camptothecin that are used to treat various neoplastic diseases involve substitutions at positions C-7, C-9, and C-11 of the basic molecule. All analogues as well as the parent molecule bind to topoisomerase 1 and interfere with its functions during DNA replication. 

Eukaryotic cells also have type 1 and type 11 topoisomerases. The type 1 enzymes are topoisomerases 1 and 111 the type 11 enzymes are topoisomerases 11a and 11/3. The eukaryotic type 11 topoisomerases cannot underwind DNA (introduce negative supercoils), but they can relax both positive and negative supercoils. We consider one probable origin of negative supercoils in eukaryotic cells in our discussion of chromatin in Section 24.3. The process catalyzed by eukaryotic type 11 topoisomerases is illustrated in Figure 24-22. 

Keshelava, N., Groshen, S., and Reynolds, C.R., Cross-resistance of topoisomerase 1 and II inhibitors in neuroblastoma cell lines. Cancer Chemother. Pharmacol, 45 (1), 1-8, 2000. 

The compound berberine has been shown to exhibit a number of bioactivities including cytotoxicity in cancer cell lines (Kettmann et al. 2004 Kim et al. 2005 Orfila et al. 2000) and topoisomerase 1 and 11 inhibition (Kim et al. 1998 Mantena et al. 2006 Pasqual et al. 1993). Studies have indicated that the antimicrobial action of berberine may be potentiated by non-antimicrobial compounds found in berberine-containing plants, indicating a synergistic action of compounds (Stermitz et al. 2000). 

Beta-carboline alkaloids from Gallant he thalictroides (Rubiaceae) are reported to inhibit DNA topoisomerases 1 and 11. ... 

Figueiredo PD, Perdomo RT, Garcez FR, Matos MDC, de Carvalho JE, Garcez WS. Further constituents of galianthe thalictroides (Rubiaceae) and inhibition of DNA topoisomerases 1 and 11 alpha by its cytotoxic beta-carboline alkaloids. Bioorg Med Chem Lett 2014 24(5) 1358-61. 

Larsen AK, Grondard L, Couprie J, Desoize B, Comoe L, JardilUer JC, et al. The antileukemic alkaloid fagaronine is an inhibitor of DNA topoisomerases 1 and 11. Biochem Pharmacol 1993 46 1403-12. 

C. Ballot, A. Martoriati, M. Jendoubi, S. Buche, P. Formstecher, L. Mortier, J. Kluza, and P. Marchetti, Another facet to the anticancer response to lamellarin D induction of cellular senescence through inhibition of topoisomerase 1 and intracellular Ros production. Afor. Drugs, 12 (2014) 779-98. 

Umemura, K., Yanase, K., Suzuki, M., Okutani, K., Yamori, T, and Andoh, T. (2003) Inhibition of DNA topoisomerases 1 and 11, and growth inhibition of human cancer cell lines by a marine microalgal polysaccharide. Biochem. Pharmacol., 66, 481-487. 

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