Publication
Naphtho[2,3-d]isoxazole-4,9-dione-3-carboxylates
| dc.contributor.author | Santos, Daniela M. | |
| dc.contributor.author | Santos, Maria M. M. | |
| dc.contributor.author | Viana, Ricardo J. S. | |
| dc.contributor.author | Castro, Rui E. | |
| dc.contributor.author | Moreira, Rui | |
| dc.contributor.author | Rodrigues, Cecilia M. R. | |
| dc.date.accessioned | 2015-12-30T10:18:11Z | |
| dc.date.available | 2015-12-30T10:18:11Z | |
| dc.date.issued | 2009 | |
| dc.description.abstract | Compounds containing a quinone moiety represent an important class of biologically active molecules that are widespread in nature, displaying anticancer, antibacterial, antimalarial, and fungicidal activities. In the course of designing 2,3-disubstituted-1,4-naphthoquinones derivatives as potential cysteine protease inhibitors, two naphtho[2,3-d]isoxazole-4,9-dione-3-carboxylates, 1a and 1b, were obtained. The antiapoptotic potential of 1a and 1b was then evaluated and compared to that of naphthoquinone 4. Primary rat hepatocytes were incubated with synthesized naphthoquinone derivatives and then exposed to the apoptotic stimulus camptothecin. Our results indicate that naphthol 2,3-dlisoxazole-4,9-dione-3-carboxylates 1a and 1b exerted a potent protective role in camptothecin-induced apoptosis in primary rat hepatocytes. Both 1a and 1b significantly increased cell viability, while reducing nuclear fragmentation, caspase-3, -8 and -9 activation, and cytochrome c release induced by camptothecin. In addition, 1a and 1b were shown to up-regulate Bcl-X-L, a pro-survival member of the Bcl-2 family of proteins, which modulates the mitochondrial pathway of apoptosis. Similar protective effects of quinone derivatives were seen in HuH-7 and PC12 cells incubated with distinct apoptotic stimuli, such as camptothecin, TGF-beta 1, or rotenone. Our results suggest that naphtho[2,3-d]isoxazole-4,9-dione-3-carboxylates 1a and 1b may act as potent, cytoprotective agents, through modulation of apoptotic pathways. (C) 2009 Elsevier Ireland Ltd. All rights reserved.. - Fundacao para a Ciencia e a Tecnologia (Portugal) [PTDC/SAU-FCF/67912/2006]. - This work was supported by Fundacao para a Ciencia e a Tecnologia (Portugal) through grant PTDC/SAU-FCF/67912/2006 (C.M.P.R.), and doctoral fellowships to D.M.S. and RJ.S.V. and postdoctoral fellowships to M.M.M.S. and R.E.C. | |
| dc.format | application/pdf | |
| dc.identifier.citation | CHEMICO-BIOLOGICAL INTERACTIONS. - Vol. 180, n. 2 (2009), p. 175-182 | |
| dc.identifier.doi | http://dx.doi.org/10.1016/j.cbi.2009.03.007 | |
| dc.identifier.issn | 0009-2797 | |
| dc.identifier.uri | http://hdl.handle.net/10451/21461 | |
| dc.language.iso | eng | |
| dc.publisher | ELSEVIER IRELAND LTD | |
| dc.subject | Biochemistry & Molecular Biology | |
| dc.subject | Pharmacology & Pharmacy | |
| dc.subject | Toxicology | |
| dc.title | Naphtho[2,3-d]isoxazole-4,9-dione-3-carboxylates | |
| dc.title | Potent, non-cytotoxic, antiapoptotic agents | |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.endPage | 182 | por |
| oaire.citation.startPage | 175 | por |
| oaire.citation.title | CHEMICO-BIOLOGICAL INTERACTIONS | por |
| oaire.citation.volume | Vol. 180 | por |
| rcaap.rights | restrictedAccess | |
| rcaap.type | article |