A review of the newer aromatase inhibitors in the management of metastatic breast cancer

Reddy, Pavan S.

doi:10.1046/j.1365-2710.1998.00145.x

Cited by 10 publications

(6 citation statements)

References 27 publications

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“…The World Health Organization has estimated that more than 1.2 million people will be diagnosed with breast cancer this year worldwide, including more than 180 000 in the United States . The role of estrogens in the development of breast cancer is well established, with the majority of postmenopausal women having hormone receptor-positive tumors. − One strategy for the treatment of these cancers is to decrease estrogen production. , Aromatase, a key cytochrome P450 enzyme, catalyzes the rate-limiting aromatization step for the conversion of androgens (testosterone and androstenedione) to estrogens (estradiol and estrone) . This pathway is the main source of estrogen in postmenopausal women.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of (±)-Abyssinone II and Its Analogues as Aromatase Inhibitors for Chemoprevention of Breast Cancer

et al. 2007

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An efficient and economical synthesis of the naturally occurring aromatase inhibitor abyssinone II was performed. The synthesis features an optimized aromatic prenylation reaction in which an arylcopper intermediate is reacted with prenyl bromide to afford a key intermediate that was converted to a prenylated aromatic aldehyde. Condensation of the aldehyde with an o-hydroxyacetophenone under Claisen-Schmidt conditions afforded a chalcone that was deprotected and cyclized in the presence of sodium acetate in refluxing ethanol to afford (+/-)-abyssinone II. The synthesis proved to be versatile enough to provide an array of abyssinone II derivatives that were evaluated as aromatase inhibitors. Methylation of the 4'-hydroxyl group of (+/-)-abyssinone II resulted in a significant increase in aromatase inhibitory activity, and further smaller increases in activity resulted from the methylation of the 7-hydroxyl group and removal of the prenyl side chain. As a result of these structural changes, the most active flavanone of the series was 20 times more potent than (+/-)-abyssinone II (IC50 40.95 microM).

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Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of (±)-Abyssinone II and Its Analogues as Aromatase Inhibitors for Chemoprevention of Breast Cancer

et al. 2007

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“…Epidemiological and experimental evidence strongly support a role for estrogens in the development and growth of breast cancer. 1,2 Similarly, the participation of estrogens in prostate neoplasia has been postulated. 3,4 Therefore, one chemotherapeutic or chemopreventive strategy for breast and prostate cancer control is to decrease estrogen production.…”

mentioning

confidence: 99%

“…Epidemiological and experimental evidence strongly support a role for estrogens in the development and growth of breast cancer. , Similarly, the participation of estrogens in prostate neoplasia has been postulated. , Therefore, one chemotherapeutic or chemopreventive strategy for breast and prostate cancer control is to decrease estrogen production . Accordingly, inhibition of aromatase, an enzyme that catalyzes the final, rate-limiting step in estrogen biosynthesis, is being explored as a target germane to the treatment or prevention of breast and prostate cancers …”

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confidence: 99%

“…Bioassay-guided fractionation of the ethyl acetate-soluble extract of B. papyrifera using this assay led to the isolation of five new (1,(8)(9)(10)(11) and 10 known (12)(13)(14)(15)(16)(17)(18)(19)(20)(21) compounds that were found to be active. Additionally, six new compounds (2)(3)(4)(5)(6)(7) and 21 known compounds were isolated and characterized as inactive when evaluated with this in vitro aromatase assay. 25,26 We currently report the isolation and identification of active and/or new compounds using the aromatase inhibition assay to guide chromatographic purification and describe structure- activity relationships among the various compound classes obtained.…”

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Aromatase Inhibitors from Broussonetia papyrifera

et al. 2001

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Bioassay-guided fractionation of an ethyl acetate-soluble extract from the whole plants of Broussonetia papyrifera, using an in vitro aromatase inhibition assay, led to the isolation of five new active compounds, 5,7,2',4'-tetrahydroxy-3-geranylflavone (1), isogemichalcone C (8), 3'-[gamma-hydroxymethyl-(E)-gamma-methylallyl]-2,4,2',4'-tetrahydroxychalcone 11'-O-coumarate (9), demethylmoracin I (10), and (2S)-2',4'-dihydroxy-2' '-(1-hydroxy-1-methylethyl)dihydrofuro[2,3-h]flavanone (11), and 10 known (12-21) compounds which were also found to be active. Of these compounds, the most potent were 9 (IC(50) 0.5 microM), 11 (IC(50) 0.1 microM), isolicoflavonol (12, IC(50) 0.1 microM), and (2S)-abyssinone II (13, IC(50) 0.4 microM). Additionally, six new compounds, 5,7,3',4'-tetrahydroxy-6-geranylflavonol (2), 5,7,3',4'-tetrahydroxy-3-methoxy-6-geranylflavone (3), (2S)-7,4'-dihydroxy-3'-prenylflavan (4), 1-(2,4-dihydroxyphenyl)-3-(4-hydroxyphenyl)propane (5), 1-(2,4-dihydroxy-3-prenylphenyl)-3-(4-hydroxyphenyl)propane (6), and 1-(4-hydroxy-2-methoxyphenyl)-3-(4-hydroxy-3-prenylphenyl)propane (7), were isolated and characterized, but proved to be inactive as aromatase inhibitors, as were an additional 21 known compounds. The structures of the new compounds (1-11) were elucidated by spectroscopic methods. Structure-activity relationships in the aromatase assay were determined for the benzofurans, biphenylpropanoids, coumarins, and various types of flavonoids (chalcones, flavans, flavanones, and flavones) obtained among a total of 42 constituents of B. papyrifera.

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“…Although it was found to be effective and produce few adverse effects in preliminary studies, clinical data related to plomestane are very scarce because of the "technical problems" that were encountered in the course of its development. 36 …”

Section: C-19 Modified Substrate Analogsmentioning

confidence: 99%

Anticancer Drugs That Modulate Hormone Action

Avendaño¹,

Menéndez²

2015

Medicinal Chemistry of Anticancer Drugs

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A review of the newer aromatase inhibitors in the management of metastatic breast cancer

Abstract: The newer aromatase inhibitors have several advantages compared to aminoglutethimide and are a useful addition to the armamentarium of therapies employed in the palliative management of advanced breast cancer.

Cited by 10 publications

References 27 publications

Synthesis and Biological Evaluation of (±)-Abyssinone II and Its Analogues as Aromatase Inhibitors for Chemoprevention of Breast Cancer

Synthesis and Biological Evaluation of (±)-Abyssinone II and Its Analogues as Aromatase Inhibitors for Chemoprevention of Breast Cancer

Aromatase Inhibitors from Broussonetia papyrifera

Anticancer Drugs That Modulate Hormone Action

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