Dihydroxyxanthones prenylated derivatives: Synthesis, structure elucidation, and growth inhibitory activity on human tumor cell lines with improvement of selectivity for MCF-7

Castanheiro, Raquel A. P.; Pinto, Madalena; Silva, Artur M. S.; Cravo, Sara; Gales, Luı́s; Damas, Ana M.; Nazareth, Naïr; Nascimento, María Säo José; Eaton, G. R.

doi:10.1016/j.bmc.2007.06.037

Cited by 45 publications

(41 citation statements)

References 18 publications

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“…Earlier workers [9], [10], [11], [12], [13] have reported the cytotoxicity of rubraxanthone (2) against several human cancer cell lines. In line with a previous article from our laboratory [14] which discussed the literature and our own work on xanthones as inhibitors of the growth of human cancer cell lines and, in particular, our more recent study of the effect of some O-and C-prenylated xanthones [15], xanthones 1-4 and compound 5 were evaluated for their capacity to inhibit the growth of four human cell lines MCF-7 (breast ER+), MDA-MB-231 (breast ER-), NCI-H460 (lung) and SF-268 (glioma) which are different from the cell lines studied earlier in the case of rubraxanthone. The results are shown in • " Table 1.…”

supporting

confidence: 83%

Cytotoxicity of Prenylated Xanthones and Other Constituents from the Wood ofGarcinia merguensis

Kijjoa¹,

González²,

Pinto³

et al. 2008

Planta Med

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One new prenylated xanthone 5-farnesyltoxyloxanthone B ( 4), three known xanthones alpha-mangostin ( 1), rubraxanthone ( 2) and isocowanol ( 3) as well as (2 E,6 E,10 E)-4beta-hydroxy-3-methyl-5beta-(3,7,11,15-tetramethylhexadeca-2,6,10-tetraenyl)-cyclohex-2-en-1-one ( 5) and 3,3',4- O-trimethylellagic acid were isolated from the wood of GARCINIA MERGUENSIS Wight. The cytotoxic activities of compounds 1 - 5 were evaluated against the MCF-7, MDA-MB-231, NCI-H-460 and SF-268 cell lines with rubraxanthone 2 and 5 exhibiting the highest activity at 9.0 and 12.1 microM, respectively, against MCF-7 cells.

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supporting

confidence: 83%

Cytotoxicity of Prenylated Xanthones and Other Constituents from the Wood ofGarcinia merguensis

Kijjoa¹,

González²,

Pinto³

et al. 2008

Planta Med

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“…A major obstacle to the clinical use of wt-p53 activators is the acquisition of p53 mutations during treatment [146]. Maki and coworkers demonstrated that wt-p53-harboring cancers lead to resistant clones with acquired p53 mutations, if chronically treated with nutlin-3a [131].…”

Section: Small Molecules: New Opportunities With Challengesmentioning

confidence: 99%

“…It is also possible that activation of p53 may lead to senescence, but not apoptosis, which could be hazardous in long term use [146]. Mirzayans et al supported this assertion that the primary response to p53 activation in wt-p53 cancer cells may represent a form of senescence [148].…”

Section: Small Molecules: New Opportunities With Challengesmentioning

confidence: 99%

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The role of p53 in cancer drug resistance and targeted chemotherapy

et al. 2016

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Cancer has long been a grievous disease complicated by innumerable players aggravating its cure. Many clinical studies demonstrated the prognostic relevance of the tumor suppressor protein p53 for many human tumor types. Overexpression of mutated p53 with reduced or abolished function is often connected to resistance to standard medications, including cisplatin, alkylating agents (temozolomide), anthracyclines, (doxorubicin), antimetabolites (gemcitabine), antiestrogenes (tamoxifen) and EGFR-inhibitors (cetuximab). Such mutations in the TP53 gene are often accompanied by changes in the conformation of the p53 protein. Small molecules that restore the wild-type conformation of p53 and, consequently, rebuild its proper function have been identified. These promising agents include PRIMA-1, MIRA-1, and several derivatives of the thiosemicarbazone family. In addition to mutations in p53 itself, p53 activity may be also be impaired due to alterations in p53s regulating proteins such as MDM2. MDM2 functions as primary cellular p53 inhibitor and deregulation of the MDM2/p53-balance has serious consequences. MDM2 alterations often result in its overexpression and therefore promote inhibition of p53 activity. To deal with this problem, a judicious approach is to employ MDM2 inhibitors. Several promising MDM2 inhibitors have been described such as nutlins, benzodiazepinediones or spiro-oxindoles as well as novel compound classes such as xanthone derivatives and trisubstituted aminothiophenes. Furthermore, even naturally derived inhibitor compounds such as a-mangostin, gambogic acid and siladenoserinols have been discovered. In this review, we discuss in detail such small molecules that play a pertinent role in affecting the p53-MDM2 signaling axis and analyze their potential as cancer chemotherapeutics.

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“…Molecular modifications on the tricyclic xanthone scaffold developed in the research group led previously to interesting inhibitors of the growth of tumor cell lines Castanheiro et al, 2007;Sousa et al, 2002;Sousa et al, 2009;Palmeira et al, 2010). Particularly, prenylated xanthone derivatives have drawn the attention due to the potency of these derivatives (Palmeira et al, 2010) or selectivity toward breast adenocarcinoma (MCF-7) (Castanheiro et al, 2007). Among naturally occurring xanthones, the prenylated derivatives are the most abundant group and also show potent antitumor effects (Pinto and Castanheiro, 2009).…”

Section: Introductionmentioning

confidence: 99%

Prenylated xanthones: antiproliferative effects and enhancement of the growth inhibitory action of 4-hydroxytamoxifen in estrogen receptor-positive breast cancer cell line

et al. 2011

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The effects of three prenylated xanthones on the in vitro growth of estrogen-dependent ER (?) MCF-7 (breast), estrogen-independent ER (-) MDA-MB-231 cells (breast), and NCI-H460 (non-small cell lung) were investigated in a complete and/or steroid-free medium. 3,4-Dihydro-12-hydroxy-2,2-dimethyl-2H,6H-pyrano[3,2-b]xanthen-6-one (4), the most potent against the ER(?) MCF-7 cell line (GI 50 = 5 lM), showed an enhancement in the anti-estrogenic effect of 4-hydroxytamoxifen in this ER(?) cell line.

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Dihydroxyxanthones prenylated derivatives: Synthesis, structure elucidation, and growth inhibitory activity on human tumor cell lines with improvement of selectivity for MCF-7

Cited by 45 publications

References 18 publications

Cytotoxicity of Prenylated Xanthones and Other Constituents from the Wood ofGarcinia merguensis

Cytotoxicity of Prenylated Xanthones and Other Constituents from the Wood ofGarcinia merguensis

The role of p53 in cancer drug resistance and targeted chemotherapy

Prenylated xanthones: antiproliferative effects and enhancement of the growth inhibitory action of 4-hydroxytamoxifen in estrogen receptor-positive breast cancer cell line

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