Genomes and Genes
topoisomerase ii inhibitors
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.
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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
- 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 pubmedBisdioxopiperazines 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...
- 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. ..
- 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 publisherIt 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...
- 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. ..
- 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. ..
- 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 publisherGlucocorticoids (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...
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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...
- 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
- 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. ..
- 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. ..
- Grand R, Stewart G. Alchemix, p53 and topoisomerase. Aging (Albany NY). 2015;7:601-2 pubmed
- 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. ..
- 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) ..
- 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
- 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. ..
- 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. ..
- 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. ..
- Vassetzky Y, Alghisi G, Gasser S. DNA topoisomerase II mutations and resistance to anti-tumor drugs. Bioessays. 1995;17:767-74 pubmed
- 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. ..