topoisomerase ii inhibitors

Summary

Summary: Compounds that inhibit the activity of DNA TOPOISOMERASE II. Included in this category are a variety of ANTINEOPLASTIC AGENTS which target the eukaryotic form of topoisomerase II and ANTIBACTERIAL AGENTS which target the prokaryotic form of topoisomerase II.

Top Publications

  1. Permana P, Snapka R, Shen L, Chu D, Clement J, Plattner J. Quinobenoxazines: a class of novel antitumor quinolones and potent mammalian DNA topoisomerase II catalytic inhibitors. Biochemistry. 1994;33:11333-9 pubmed
    ..complex is not necessary for the antitumor activity of this class of quinolones and that the catalytic inhibition of DNA topoisomerase II may contribute significantly to the anticancer activity of other DNA topoisomerase II inhibitors.
  2. Li P, Jiang H, Zhang W, Li Y, Zhao M, Zhou W, et al. Synthesis of carbazole derivatives containing chalcone analogs as non-intercalative topoisomerase II catalytic inhibitors and apoptosis inducers. Eur J Med Chem. 2018;145:498-510 pubmed publisher
    ..It was further confirmed by Annexin-V-FITC binding assay. Western blot analysis revealed that compound 3h induces apoptosis likely through the activation of caspase proteins. ..
  3. Austin C, Patel S, Ono K, Nakane H, Fisher L. Site-specific DNA cleavage by mammalian DNA topoisomerase II induced by novel flavone and catechin derivatives. Biochem J. 1992;282 ( Pt 3):883-9 pubmed
    ..These results are discussed in regard to the selectivity of antiviral agents. ..
  4. Simard O, Niavarani S, Gaudreault V, Boissonneault G. Torsional stress promotes trinucleotidic expansion in spermatids. Mutat Res. 2017;800-802:1-7 pubmed publisher
    ..The transient increase in torsional stress during spermiogenesis may therefore provide an ideal context for the generation of such secondary DNA structures leading to the paternal anticipation of trinucleotidic diseases. ..
  5. Kozuki T, Chikamori K, Surleac M, Micluta M, Petrescu A, Norris E, et al. Roles of the C-terminal domains of topoisomerase II? and topoisomerase II? in regulation of the decatenation checkpoint. Nucleic Acids Res. 2017;45:5995-6010 pubmed publisher
    ..Together these results suggest that topo II? and topo II? cooperate to maintain genome stability, which may be distinctly modulated by their CTDs. ..
  6. Zhang J, Ito H, Hino M, Kimura M. A RelE/ParE superfamily toxin in Vibrio parahaemolyticus has DNA nicking endonuclease activity. Biochem Biophys Res Commun. 2017;489:29-34 pubmed publisher
    ..To our knowledge, Vp1843 is the first toxin with DNA nicking endonuclease activity among the RelE/ParE toxin superfamily. ..
  7. Allison S, Sadiq M, Baronou E, Cooper P, Dunnill C, Georgopoulos N, et al. Preclinical anti-cancer activity and multiple mechanisms of action of a cationic silver complex bearing N-heterocyclic carbene ligands. Cancer Lett. 2017;403:98-107 pubmed publisher
    ..Thus, Ag8 targets multiple pathways of importance in cancer biology, is less active against non-cancer cells and shows activity in vivo in a loco-regional setting. ..
  8. Ashley R, Lindsey R, McPherson S, Turnbough C, Kerns R, Osheroff N. Interactions between Quinolones and Bacillus anthracis Gyrase and the Basis of Drug Resistance. Biochemistry. 2017;56:4191-4200 pubmed publisher
  9. Mitton Fry M, Brickner S, Hamel J, Barham R, Brennan L, Casavant J, et al. Novel 3-fluoro-6-methoxyquinoline derivatives as inhibitors of bacterial DNA gyrase and topoisomerase IV. Bioorg Med Chem Lett. 2017;27:3353-3358 pubmed publisher
    ..aureus strains with mutations conferring resistance to NBTIs. Compound 14 also displayed an improved hERG IC50 of 85.9?M and a favorable profile in the anesthetized guinea pig model. ..

More Information

Publications48

  1. Li D, Yuan Z, Chen S, Zhang C, Song L, Gao C, et al. Synthesis and biological research of novel azaacridine derivatives as potent DNA-binding ligands and topoisomerase II inhibitors. Bioorg Med Chem. 2017;25:3437-3446 pubmed publisher
    ..Later study indicated that all the compounds displayed topoisomerases II inhibition activity at 50?M. The representative compound 9 could bind with DNA and induce U937 apoptosis through the exogenous pathway. ..
  2. Hosoe Nagai Y, Hidaka T, Sonoda A, Sasaki Y, Yamamoto Nonaka K, Seki T, et al. Re-expression of Sall1 in podocytes protects against adriamycin-induced nephrosis. Lab Invest. 2017;97:1306-1320 pubmed publisher
    ..These protective aspects of Sall1 re-expression in injured podocytes may have the potential to reduce apoptosis and possibly glomerulosclerosis. ..
  3. Shimizu S, Eguchi Y, Kamiike W, Waguri S, Uchiyama Y, Matsuda H, et al. Bcl-2 blocks loss of mitochondrial membrane potential while ICE inhibitors act at a different step during inhibition of death induced by respiratory chain inhibitors. Oncogene. 1996;13:21-9 pubmed
    ..The ICE family proteases act at a different step other than the loss of mitochondrial membrane potential. ..
  4. Han X, Zhong Y, Zhou G, Qi H, Li S, Ding Q, et al. Synthesis and biological evaluation of N-(carbobenzyloxy)-l-phenylalanine and N-(carbobenzyloxy)-l-aspartic acid-?-benzyl ester derivatives as potent topoisomerase II? inhibitors. Bioorg Med Chem. 2017;25:3116-3126 pubmed publisher
    ..The results indicated that these compounds could serve as promising leads for further optimization as novel antitumor agents. ..
  5. Kammari K, Devaraya K, Bommakanti A, Kondapi A. Development of pyridine dicoumarols as potent anti HIV-1 leads, targeting HIV-1 associated topoisomeraseII? kinase. Future Med Chem. 2017;9:1597-1609 pubmed publisher
    ..A new class of anti-HIV-1 lead compounds have been designed and tested. Further studies would result in development of  novel and potential drugs. ..
  6. Mahbub A, Le Maitre C, Haywood Small S, Cross N, Jordan Mahy N. Glutathione is key to the synergistic enhancement of doxorubicin and etoposide by polyphenols in leukaemia cell lines. Cell Death Dis. 2015;6:e2028 pubmed publisher
  7. Zhao G, Lan D, Qi G. Design and development of some thiazole-based flavanoids as novel antibacterial against pathogens causing surgical site infection for possible benefit in bone trauma via inhibition of DNA gyrase. Chem Biol Drug Des. 2017;90:778-790 pubmed publisher
    ..The hemolytic activity of the potent compounds showed mild to no activity together with excellent pharmacokinetics, suggesting to have a potential for the development of designed compounds as novel antibacterial agents. ..
  8. Ichikawa Y, Ghanefar M, Bayeva M, Wu R, Khechaduri A, Naga Prasad S, et al. Cardiotoxicity of doxorubicin is mediated through mitochondrial iron accumulation. J Clin Invest. 2014;124:617-30 pubmed publisher
    ..These results suggest that the cardiotoxic effects of doxorubicin develop from mitochondrial iron accumulation and that reducing mitochondrial iron levels protects against doxorubicin-induced cardiomyopathy. ..
  9. D ARPA P, Beardmore C, Liu L. Involvement of nucleic acid synthesis in cell killing mechanisms of topoisomerase poisons. Cancer Res. 1990;50:6919-24 pubmed
    ..This antagonistic effect between topoisomerase I and II poisons could be explained by the strong inhibitory effect of camptothecin on RNA transcription. ..
  10. Shen L, Kohlbrenner W, Weigl D, Baranowski J. Mechanism of quinolone inhibition of DNA gyrase. Appearance of unique norfloxacin binding sites in enzyme-DNA complexes. J Biol Chem. 1989;264:2973-8 pubmed
  11. Jensen L, Nitiss K, Rose A, Dong J, Zhou J, Hu T, et al. A novel mechanism of cell killing by anti-topoisomerase II bisdioxopiperazines. J Biol Chem. 2000;275:2137-46 pubmed
    Bisdioxopiperazines are a unique class of topoisomerase II inhibitors that lock topoisomerase II at a point in the enzyme reaction cycle where the enzyme forms a closed clamp around DNA...
  12. Bennett M, MacDonald K, Chan S, Luzio J, Simari R, Weissberg P. Cell surface trafficking of Fas: a rapid mechanism of p53-mediated apoptosis. Science. 1998;282:290-3 pubmed
    ..In contrast, lpr and gld fibroblasts were resistant to p53-induced apoptosis. Thus, p53 can mediate apoptosis through Fas transport from cytoplasmic stores. ..
  13. Minniti E, Byl J, Riccardi L, Sissi C, Rosini M, De Vivo M, et al. Novel xanthone-polyamine conjugates as catalytic inhibitors of human topoisomerase IIα. Bioorg Med Chem Lett. 2017;27:4687-4693 pubmed publisher
    It has been proposed that xanthone derivatives with anticancer potential act as topoisomerase II inhibitors because they interfere with the ability of the enzyme to bind its ATP cofactor...
  14. Picconi P, Hind C, Jamshidi S, Nahar K, Clifford M, Wand M, et al. Triaryl Benzimidazoles as a New Class of Antibacterial Agents against Resistant Pathogenic Microorganisms. J Med Chem. 2017;60:6045-6059 pubmed publisher
    ..The MOA was further supported by the molecular modeling study. ..
  15. Shen L, Pernet A. Mechanism of inhibition of DNA gyrase by analogues of nalidixic acid: the target of the drugs is DNA. Proc Natl Acad Sci U S A. 1985;82:307-11 pubmed
    ..The calculated apparent Kd values of these analogues correlate well with their Ki values, providing strong evidence that the binding affinity of the drug to DNA determines biological potency. ..
  16. Qattan M, Bakker E, Rajendran R, Chen D, Saha V, Liu J, et al. Differential regulation of cell death pathways by the microenvironment correlates with chemoresistance and survival in leukaemia. PLoS ONE. 2017;12:e0178606 pubmed publisher
    Glucocorticoids (GCs) and topoisomerase II inhibitors are used to treat acute lymphoblastic leukaemia (ALL) as they induce death in lymphoid cells through the glucocorticoid receptor (GR) and p53 respectively...
  17. Bist G, Park S, Song C, Thapa Magar T, Shrestha A, Kwon Y, et al. Dihydroxylated 2,6-diphenyl-4-chlorophenylpyridines: Topoisomerase I and II? dual inhibitors with DNA non-intercalative catalytic activity. Eur J Med Chem. 2017;133:69-84 pubmed publisher
  18. Wu Y, Hong C, Wang Y, Huang W, Yeh Y, Wang B, et al. A novel histone deacetylase inhibitor TMU-35435 enhances etoposide cytotoxicity through the proteasomal degradation of DNA-PKcs in triple-negative breast cancer. Cancer Lett. 2017;400:79-88 pubmed publisher
    ..Taken together, our data suggest that TMU-35435 enhances etoposide cytotoxicity by regulating ubiquitin-proteasome system and inhibiting the DNA repair pathway in TNBC. ..
  19. Kim E, Kim S, Kim S, Lee M. A novel topoisomerase 2a inhibitor, cryptotanshinone, suppresses the growth of PC3 cells without apparent cytotoxicity. Toxicol Appl Pharmacol. 2017;330:84-92 pubmed publisher
    ..Collectively, our findings support the development of cryptotanshinone as a promising candidate for treating cancer by targeting topoisomerase 2a. ..
  20. Zdraljevic S, Strand C, Seidel H, Cook D, Doench J, Andersen E. Natural variation in a single amino acid substitution underlies physiological responses to topoisomerase II poisons. PLoS Genet. 2017;13:e1006891 pubmed publisher
    ..These results explain why hTOPII? and hTOPII? are differentially affected by various poisons and demonstrate the utility of C. elegans in understanding the genetics of drug responses. ..
  21. Elsea S, Osheroff N, Nitiss J. Cytotoxicity of quinolones toward eukaryotic cells. Identification of topoisomerase II as the primary cellular target for the quinolone CP-115,953 in yeast. J Biol Chem. 1992;267:13150-3 pubmed
    ..These results strongly suggest that topoisomerase II is the primary physiological target responsible for quinolone cytotoxicity and that CP-115,953 kills cells by converting the type II enzyme into a cellular poison. ..
  22. Nishi K, Kato M, Sakurai S, Matsumoto A, Iwase Y, Yumita N. Enoxacin with UVA Irradiation Induces Apoptosis in the AsPC1 Human Pancreatic Cancer Cell Line Through ROS Generation. Anticancer Res. 2017;37:6211-6214 pubmed
    ..Therefore, the combination of enoxacin with mild UVA irradiation may be a useful method for treating pancreatic cancer...
  23. Sosic A, Zuravka I, Schmitt N, Miola A, Göttlich R, Fabris D, et al. Direct and Topoisomerase?II Mediated DNA Damage by Bis-3-chloropiperidines: The Importance of Being an Earnest G. ChemMedChem. 2017;12:1471-1479 pubmed publisher
  24. Walker S, Labroli M, Painter R, Wiltsie J, Sherborne B, Murgolo N, et al. Antibacterial small molecules targeting the conserved TOPRIM domain of DNA gyrase. PLoS ONE. 2017;12:e0180965 pubmed publisher
  25. Wolfson J, Hooper D. The fluoroquinolones: structures, mechanisms of action and resistance, and spectra of activity in vitro. Antimicrob Agents Chemother. 1985;28:581-6 pubmed
  26. Tanaka M, Zhang Y, Ishida H, Akasaka T, Sato K, Hayakawa I. Mechanisms of 4-quinolone resistance in quinolone-resistant and methicillin-resistant Staphylococcus aureus isolates from Japan and China. J Med Microbiol. 1995;42:214-9 pubmed
    ..Thus the mechanisms of 4-quinolone-resistance in these MRSA isolates involved alterations in both DNA gyrase and antimicrobial uptake and efflux. ..
  27. Elsea S, McGuirk P, Gootz T, Moynihan M, Osheroff N. Drug features that contribute to the activity of quinolones against mammalian topoisomerase II and cultured cells: correlation between enhancement of enzyme-mediated DNA cleavage in vitro and cytotoxic potential. Antimicrob Agents Chemother. 1993;37:2179-86 pubmed
    ..This correlation strongly suggests that these quinolones promote cell death by converting topoisomerase II to a cellular poison. ..
  28. Machowicz R, Janka G, Wiktor Jedrzejczak W. Your critical care patient may have HLH (hemophagocytic lymphohistiocytosis). Crit Care. 2016;20:215 pubmed publisher
  29. Grand R, Stewart G. Alchemix, p53 and topoisomerase. Aging (Albany NY). 2015;7:601-2 pubmed
  30. Wei Y, Diao L, Lu S, Wang H, Suo F, Dong M, et al. SUMO-Targeted DNA Translocase Rrp2 Protects the Genome from Top2-Induced DNA Damage. Mol Cell. 2017;66:581-596.e6 pubmed publisher
    ..The budding yeast homolog of Rrp2, Uls1, plays a similar role, indicating that this genome protection mechanism is widely employed, a finding with implications for cancer treatment. ..
  31. Shen L, Baranowski J, Pernet A. Mechanism of inhibition of DNA gyrase by quinolone antibacterials: specificity and cooperativity of drug binding to DNA. Biochemistry. 1989;28:3879-85 pubmed
    ..Chem. (in press)], occurs near the drug's supercoiling inhibition concentration. As shown in this paper, binding saturation curves of this type are highly cooperative (with Hill constant greater than 4).(ABSTRACT TRUNCATED AT 250 WORDS) ..
  32. Fournier B, Zhao X, Lu T, Drlica K, Hooper D. Selective targeting of topoisomerase IV and DNA gyrase in Staphylococcus aureus: different patterns of quinolone-induced inhibition of DNA synthesis. Antimicrob Agents Chemother. 2000;44:2160-5 pubmed
  33. Wang Y, Chen S, Wu C, Liao Y, Lin T, Liu K, et al. Producing irreversible topoisomerase II-mediated DNA breaks by site-specific Pt(II)-methionine coordination chemistry. Nucleic Acids Res. 2017;45:10861-10871 pubmed publisher
    ..This approach may be exploited to achieve isoform-specific targeting of human Top2s. ..
  34. Bailly C. Contemporary challenges in the design of topoisomerase II inhibitors for cancer chemotherapy. Chem Rev. 2012;112:3611-40 pubmed publisher
  35. Shen L, Mitscher L, Sharma P, O Donnell T, Chu D, Cooper C, et al. Mechanism of inhibition of DNA gyrase by quinolone antibacterials: a cooperative drug--DNA binding model. Biochemistry. 1989;28:3886-94 pubmed
    ..Supporting evidence for and implications of this model are provided. ..
  36. Gilad Y, Tuchinsky H, Ben David G, Minnes R, Gancz A, Senderowitz H, et al. Discovery of potent molecular chimera (CM358) to treat human metastatic melanoma. Eur J Med Chem. 2017;138:602-615 pubmed publisher
    ..In a human metastatic melanoma (WM 266-4) xenograft model, this compound was profoundly superior to a mixture of AM and CLB in reduction of tumor growth, maintenance of body weight and extension of overall survival. ..
  37. Vassetzky Y, Alghisi G, Gasser S. DNA topoisomerase II mutations and resistance to anti-tumor drugs. Bioessays. 1995;17:767-74 pubmed
  38. Chan W, Yu J. Inhibition of UV irradiation-induced oxidative stress and apoptotic biochemical changes in human epidermal carcinoma A431 cells by genistein. J Cell Biochem. 2000;78:73-84 pubmed
    ..Collectively, our results demonstrate the involvement of oxidative stress in the UV irradiation-induced caspase activation and the subsequent apoptotic biochemical changes and show that genistein is a potent inhibitor for this process. ..
  39. Heide L. The aminocoumarins: biosynthesis and biology. Nat Prod Rep. 2009;26:1241-50 pubmed publisher