New hits as phase II enzymes inducers from a focused library with heteroatom-heteroatom and Michael-acceptor motives

Future Science OA

Volumn 1, Issue 3, 2015, Pages

  Cabrera, Mauricio ^a   Ovalle, Stefani De ^a   Bollati Fogolín, Mariela ^b   Nascimento, Fabiana ^c   Corbelini, Patrícia ^c   Janarelli, Fernanda ^c   Kawano, Daniel ^c   Eifler Lima, Vera Lucia ^c   González, Mercedes ^a   Cerecetto, Hugo ^a  

^a UNIVERSIDAD DE LA REPÚBLICA   (Uruguay)

^b INSTITUT PASTEUR DE MONTEVIDEO   (Uruguay)

^c FEDERAL UNIVERSITY OF RIO GRANDE DO SUL   (Brazil)

Author keywords

1,2,4 triazine 4 oxide; 1,2,5 oxadiazol 2 oxide; chemopreventive agents; phase II enzyme inducers; tetrahydropyrimidinone

Indexed keywords

1,2,3 THIADIAZOLE; 1,2,3,4 TETRAHYDROPYRIMIDINE DERIVATIVE; 1,2,4 OXADIAZOLE; 1,2,4 THIADIAZOLE; 1,2,5 OXADIAZOL 2 OXIDE; 1,3,4 OXATHIAZOLE; ALPHA BETA UNSATURATED CARBONYL; ALPHA BETA UNSATURATED N OXIDE; ALPHA BETA UNSATURATED OXIME; COUMARIN; ENZYME; ENZYME PRECURSOR; FURAZAN DERIVATIVE; GLUTATHIONE TRANSFERASE; OXADIAZOLE DERIVATIVE; PYRAZOLE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE (PHOSPHATE) DEHYDROGENASE (QUINONE); THIADIAZOLE DERIVATIVE; THIENYL HYDRAZONE; TRIAZINE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CANCER CHEMOTHERAPY; CARCINOGENESIS; CHEMOPROPHYLAXIS; CONFOCAL MICROSCOPY; CONTROLLED STUDY; CYTOTOXICITY ASSAY; DNA FLANKING REGION; ENZYME ACTIVITY; GENE MUTATION; HEPATOCELLULAR CARCINOMA CELL LINE; IC50; IMMUNOFLUORESCENCE; MOLECULAR LIBRARY; MOUSE; NITROSYLATION; NONHUMAN; PHARMACOPHORE; PRIORITY JOURNAL;

EID: 85004021679     PISSN: None     EISSN: 20565623     Source Type: Journal    
DOI: 10.4155/fso.15.18     Document Type: Article

References (47)

1. Cuendet M, Oteham CP, Moon RC, Pezzuto JM. Quinone reductase induction as a biomarker for cancer chemoprevention. J. Nat. Prod. 69(3), 460-463 (2006).
2. Liu RH. Potential synergy of phytochemicals in cancer prevention: mechanism of action. J. Nutr. 134(Suppl. 12), S3479-S3485 (2004).
3. Talalay P, De Long MJ, Prochaska HJ. Identification of a common chemical signal regulating the induction of enzymes that protect against chemical carcinogenesis. Proc. Natl Acad. Sci. USA 85(21), 8261-8265 (1988).
4. Duthie SJ, Collins AR, Duthie GG, Dodson VL. Quercetin and myricetin protect against hydrogen peroxide-induced DNA damage (strand breaks and oxidized pyrimidines) in human lymphocytes. Mutat. Res. 393(3), 223-231 (1997).
5. Chen C, Kong AN. Dietary chemopreventive compounds and ARE/EpRE signaling. Free Radic. Biol. Med. 36(12), 1505-1516 (2004).
6. Hotzclaw WD, Dinkova-Kostova AT, Talalay P. Protection against electrophile and oxidative stress by induction of phase 2 genes: the quest for the elusive sensor that responds to inducers. Adv. Enzyme Regul. 44, 335-367 (2004).
7. Akihisa T, Kojima N, Kikuchi T et al. Anti-inflammatory and chemopreventive effects of triterpene cinnamates and acetates from shea fat. J. Oleo Sci. 59(6), 273-280 (2010).
8. Xu C, Li CY, Kong AN. Induction of phase I, II and III drug metabolism/transport by xenobiotics. Arch. Pharm. Res. 28(3), 249-268 (2005).
9. Wondrak GT, Cabello CM, Villeneuve NF et al. Cinnamoyl-based Nrf2-activators targeting human skin cell photo-oxidative stress. Free Radic. Biol. Med. 45(4), 385-395 (2008).
10. Athar M, Back JH, Tang X et al. Resveratrol: a review of preclinical studies for human cancer prevention. Toxicol. Appl. Pharmacol. 224(3), 274-283 (2007).
11. Song LL, Kosmeder JW, Lee SK et al. Cancer chemopreventive activity mediated by 4'-bromoflavone, a potent inducer of phase II detoxification enzymes. Cancer Res. 59(3), 578-585 (1999).
12. Cabrera M, Lavaggi ML, Croce F et al. Identification of chalcones as in vivo liver monofunctional phase II enzymes inducers. Bioorg. Med. Chem. 18(14), 5391-5399 (2010).
13. Cabrera M, Simoens M, Falchi G et al. Synthetic chalcones, flavanones, and flavones as antitumoral agents: biological evaluation and structure-activity relationships. Bioorg. Med. Chem. 15(10), 3356-3367 (2007).
14. Lee YY, Westphal AH, de Haan LH, Aarts JM, Rietjens IM, van Berkel WJ. Human NAD(P)H:quinone oxidoreductase inhibition by flavonoids in living cells. Free Radic. Biol. Med. 39(2), 257-265 (2005).
15. Couto M, Cabrera M, Echeverría GA, Piro OE, González M, Cerecetto H. A serendipitous one-step conversion of 3H-1,2-dithiole-3-thione to (E)-3-[1-(alkylthio)alkylidene]-3H-1,2-dithiole: an experimental and theoretical study. Mol. Divers. 18(2), 285-294 (2014).
16. Couto M, de Ovalle S, Cabrera M, Cerecetto H, González M. Searching phase II enzymes inducers, from Michael acceptor-[1,2]dithiolethione hybrids, as cancer chemopreventive agents. Fut. Med. Chem. doi: 10.4155/ FMC.15.32 (2015) (Epub ahead of print).
17. Prochaska HJ, Talalay P. Regulatory mechanisms of monofunctional and bifunctional anticarcinogenic enzyme inducers in murine liver. Cancer Res. 48(17), 4776-4782 (1988).
18. Rojas-García C, García-Lara S, Serna-Saldivar SO, Gutiérrez-Uribe JA. Chemopreventive effects of free and bound phenolics associated to steep waters (nejayote) obtained after nixtamalization of different maize types. Plant Foods Hum. Nutr. 67(1), 94-99 (2012).
19. Hernández P, Cabrera M, Lavaggi ML et al. Discovery of new orally effective analgesic and anti-inflammatory hybrid Furoxanyl N-acylhydrazone derivatives. Bioorg. Med. Chem. 20(6), 2158-2171 (2012).
20. Martínez-Crespo FJ, Palop JA, Sáinz Y et al. 4-Cyano-2-oxo-1,2,4-oxadiazolo[2,3-a]quinoxaline 5-N-oxides. New synthetic method and reaction with alcohols. Potential cytotoxic activity. J. Heterocycl. Chem. 33(6), 1671-1677 (1996).
21. Porcal W, Hernández P, González M et al. Heteroarylnitrones as drugs for neurodegenerative diseases: synthesis, neuroprotective properties, and free radical scavenger properties. J. Med. Chem. 51(19), 6150-6159 (2008).
22. Álvarez G, Varela J, Márquez P et al. Optimization of antitrypanosomatid agents: identification of non-mutagenic drug candidates with in vivo activity. J. Med. Chem. 57(10), 3984-3999 (2014).
23. Boiani M, Merlino A, Gerpe A et al. o-Nitroanilines as major metabolic products of anti-Trypanosoma cruzi 5-phenylethenylbenzofuroxans in microsomal and cytosolic fractions of rata hepatocytes and in whole parasitic cells. Xenobiotica 39(3), 236-248 (2009).
24. Boiani M, Boiani L, Merlino A et al. Second generation of 2H-benzimidazole 1,3-dioxide derivatives as anti-trypanosomatid agents: synthesis, biological evaluation, and mode of action studies. Eur. J. Med. Chem. 44(11), 4426-4433 (2009).
25. Cerecetto H, González M, Risso M et al. 1,2,4-Triazine N-oxide derivatives: studies as potential hypoxic cytotoxins. Part III. Arch. Pharm. (Weinheim). 337(5), 271-280 (2004).
26. Vianna DR, Bubols G, Meirelles G et al. Evaluation of the antioxidant capacity of synthesized coumarins. Int. J. Mol. Sci. 13(6), 7260-7270 (2012).
27. Figueiró F, Mendes FB, Corbelini PF et al. A monastrol-derived compound, LaSOM 63, inhibits ecto-5'nucleotidase/ CD73 activity and induces apoptotic cell death of glioma cell lines. Anticancer Res. 34(4), 1837-1842 (2014).
28. Canto RFS, Bernardi A, Battastini AMO et al. Synthesis of dihydropyrimidin-2-one/thione library and cytotoxic activity against the human U138-MG and rat C6 glioma cell lines. J. Braz. Chem. Soc. 22(7), 1379-1388 (2011).
29. Schnekenburger M, Dicato M, Diederich M. Plant-derived epigenetic modulators for cancer treatment and prevention. Biotechnol. Adv. 32(6), 1123-1132 (2014).
30. Prince M, Li Y, Childers A, Itoh K, Yamamoto M, Kleiner HE. Comparison of citrus coumarins on carcinogen-detoxifying enzymes in Nrf2 knockout mice. Toxicol. Lett. 185(3), 180-186 (2009).
31. Gerpe A, Aguirre G, Boiani L et al. Indazole N-oxide derivatives as antiprotozoal agents: synthesis, biological evaluation and mechanism of action studies. Bioorg. Med. Chem. 14(10), 3467-3480 (2006).
32. Gerpe A, Piro OE, Cerecetto H, González M. Structure of indazole N1-oxide derivatives studied by x-ray, theoretical methods, 1H, 13C, 15N NMR and EI/MS. J. Mol. Struct. 871(1-3), 98-107 (2007).
33. Castro D, Boiani L, Benitez D et al. Anti-trypanosomatid benzofuroxans and deoxygenated analogues: synthesis using polymer-supported triphenylphosphine, biological evaluation and mechanism of action studies. Eur. J. Med. Chem. 44(12), 5055-5065 (2009).
34. Cerecetto H, González M, Onetto S et al. 1,2,4-triazine N-oxide and N,N'-dioxide derivatives: studies as potential hypoxic cytotoxins and DNA binder. Med. Chem. Res. 10(5), 328-337 (2001).
35. Cerecetto H, González M, Onetto S et al. 1,2,4-Triazine N-oxide derivatives: studies as potential hypoxic cytotoxins. Part II. Arch. Pharm. (Weinheim) 337(5), 247-258 (2004).
36. Stuepp CS, Figueiró F, Mendes FB et al. Activity of LaSOM 65, a monastrol-derived compound, against gliolastoma multiforme cell lines. Anticancer Res. 33(10), 4463-4468 (2013).
37. Torres BG, Uchôa F, de T, Pigatto MC et al. Pre-clinical pharmacokinetics and acute toxicological evaluation of a monastrol derivative anticancer candidate LaSOM 65 in rats. Xenobiotica 44(3), 254-263 (2014).
38. Yang Y, Cai X, Yang J et al. Chemoprevention of dietary digitoflavone on colitis-associated colon tumorigenesis through inducing Nrf2 signaling pathway and inhibition of inflammation. Mol. Cancer 13, 48 (2014).
39. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 23, 4-25 (1997).
40. Gasco A, Fruttero R, Sorba G, Di Stilo A, Calvino R. NO donors: focus on furoxan derivatives. Pure Appl. Chem. 76(5), 973-981 (2004).
41. Um HC, Jang JH, Kim DH, Lee C, Surh YJ. Nitric oxide activates Nrf2 through S-nitrosylation of Keap1 in PC12 cells. Nitric Oxide 25(2), 161-168 (2011).
42. Buckley BJ, Li S, Whorton AR. Keap1 modification and nuclear accumulation in response to S-nitrosocysteine. Free Radic. Biol. Med. 44(4), 692-698 (2008).
43. Akaike T, Fujii S, Sawa T, Ihara M. Cell signaling mediated by nitrated cyclic guanine nucleotide. Nitric Oxide 23(3), 166-174 (2010).
44. Fujii S, Sawa T, Ihara H et al. The critical role of nitric oxide signaling, via protein S-guanylation and nitrated cyclic GMP, in the antioxidant adaptive response. J. Biol. Chem. 285(31), 23970-23984 (2010).
45. Medana C, Ermondi G, Fruttero R, Di Stilo A, Ferretti C, Gasco A. Furoxans as nitric oxide donors. 4-phenyl-3-furoxancarbonitrile: thiol-mediated nitric oxide release and biological evaluation. J. Med. Chem. 37(25), 4412-4416 (1994).
46. Boiani M, Cerecetto H, González M. Cytotoxicity of furoxans: quantitative structure-activity relationships study. Farmaco 59(5), 405-412 (2004).
47. Molinspiration. www.molinspiration.com/cgi-bin/properties