Background and development of aromatase inhibitors

Miller, William R.

doi:10.1007/3-7643-7418-7_1

Cited by 9 publications

(3 citation statements)

References 99 publications

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“…To produce the estrogen deficiency in male rats, we used letrozole -a third--generation inhibitor of aromatase. The letrozole structure provides a good fit with the substrate-binding site and additionally co-ordinates with aromatase heme iron and effectively inhibits the hydroxylationa reaction necessary for aromatization [25]. Because of the ability of letrozole to reduce serum estradiol concentration, it is usually used in the treatment of estrogen-sensitive breast cancer in women [26][27][28].…”

Section: Discussionmentioning

confidence: 99%

Testis morphology in rats chronically treated with letrozole, an aromatase inhibitor

Kondarewicz¹,

Kolasa²,

Zawiślak³

et al. 2012

Folia Histochem Cytobiol.

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Abstract:The aim of this study was to investigate the influence of the long-term treatment of rats with letrozole on the testis morphology. The pharmacologically induced estrogen deficiency caused statistically significant decreases of both intratesticular and serum levels of estradiol, and morphological changes in the seminiferous epithelium and in the interstitial tissue of the testes. Six months of treatment resulted in the sloughing of premature germ cells of the seminiferous epithelium into the tubular lumen and in intraepithelial vacuolization. Multinucleated giant cells composed of premature germ cells, conglomerates of various cell nuclei and cell debris as well as irregularities and infoldings of the tubular basement membrane were also seen. Moreover, deep invaginations of the lamina propria with myoid cells were observed. Cells in the interstitial tissue showed changes similar to that observed in aging processes. The cytoplasm of LH-R-positive Leydig cells was loaded with lipofuscin granules. The number of lipofuscin-loaded cells was significantly increased in the interstitial tissue of testis in letrozole-treated rats. The results indicate the direct influence of estrogens on seminiferous tubules and the interstitial tissue morphology.

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Section: Discussionmentioning

confidence: 99%

Testis morphology in rats chronically treated with letrozole, an aromatase inhibitor

Kondarewicz¹,

Kolasa²,

Zawiślak³

et al. 2012

Folia Histochem Cytobiol.

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“…In terms of deprivation, trophic effects of oestrogen may be reduced by inhibiting biosynthesis or by blockade of hormone action [1,2]. In recent times the pharmaceutical industry has been extremely successful in developing agents such as aromatase inhibitors and anti-oestrogens [3][4][5] which efficiently and specifically affect these processes. Such drugs have advanced scientific knowledge and clinical practice in a variety of settings.…”

Section: Introductionmentioning

confidence: 99%

Molecular effects of oestrogen deprivation in breast cancer

Miller

Larionov

2011

Molecular and Cellular Endocrinology

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“…ten-fold PDE affinity (3.1 ng/mL; 6.6 nM) (Saenz De Tejada et al 2001 ). Morelloflavone was shown to inhibit phospholipase A2 at IC 50 = 0.9 µM (Gil et al 1997 ), aromatase at 3.1 µM (Recalde-Gil et al 2019 ), MAO-A at 5.1 µM (Recalde-Gil et al 2017 ), and HMG-CoA at 80.9 µM (Tuansulong et al 2011 ), which are again levels incomparable to commonly used drugs—darapladib (8.6 nM) (Hu et al 2015 ), anastrazole (Arimidex®; 15 nM) (Miller 2006 ), harmaline (2.3 nM) (Kilpatrick et al 2001 ), and mevastatin (23 nM) (Lin et al 2015 ). Since all G. kola biflavonoids are structurally related, similar affinities may be expected for all of them.…”

Section: Discussionmentioning

confidence: 99%

Garcinia kola: a critical review on chemistry and pharmacology of an important West African medicinal plant

et al. 2023

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Garcinia kola Heckel (Clusiaceae) is a tree indigenous to West and Central Africa. All plant parts, but especially the seeds, are of value in local folklore medicine. Garcinia kola is used in treatment of numerous diseases, including gastric disorders, bronchial diseases, fever, malaria and is used to induce a stimulating and aphrodisiac effect. The plant is now attracting considerable interest as a possible source of pharmaceutically important drugs. Several different classes of compounds such as biflavonoids, benzophenones, benzofurans, benzopyran, vitamin E derivatives, xanthones, and phytosterols, have been isolated from G. kola, of which many appears to be found only in this species, such as garcinianin (found in seeds and roots), kolanone (fruit pulp, seeds, roots), gakolanone (stem bark), garcinoic acid, garcinal (both in seeds), garcifuran A and B, and garcipyran (all in roots). They showed a wide range of pharmacological activities (e.g. analgesic, anticancer, antidiabetic, anti-inflammatory, antimalarial, antimicrobial, hepatoprotective and neuroprotective effects), though this has only been confirmed in animal models. Kolaviron is the most studied compound and is perceived by many studies as the active principle of G. kola. However, its research is associated with significant flaws (e.g. too high doses tested, inappropriate positive control). Garcinol has been tested under better conditions and is perhaps showing more promising results and should attract deeper research interest (especially in the area of anticancer, antimicrobial, and neuroprotective activity). Human clinical trials and mechanism-of-action studies must be carried out to verify whether any of the compounds present in G. kola may be used as a lead in the drug development.

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Background and development of aromatase inhibitors

Cited by 9 publications

References 99 publications

Testis morphology in rats chronically treated with letrozole, an aromatase inhibitor

Testis morphology in rats chronically treated with letrozole, an aromatase inhibitor

Molecular effects of oestrogen deprivation in breast cancer

Garcinia kola: a critical review on chemistry and pharmacology of an important West African medicinal plant

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