Aromatase, catalyzing final step of estrogen biosynthesis, is considered a key target for the development of drug against estrogen-dependent breast cancer (EDBC). Identification and development of naturally occurring compounds, such as flavonoids, as drugs against EDBC is in demand due to their lesser toxicity when compared to those of synthetic ones. Thus, a three-dimensional quantitative stru...

4-Hydroxyandrostenedione (4-OHA) is a more potent and specific inhibitor of aromatase (estrogen synthetase) than aminoglutethimide (AG). The two inhibitors were compared in rats with 7,12-dimethylbenz(a)anthracene-induced, hormone-dependent tumors and in normal cyclic rats treated for 4 and 2 weeks, respectively. Ovarian estradiol levels and aromatase activities were not consistently reduced, a...

A series of 2-amino(chloro)-3-chloro-1,4-naphthoquinone derivatives (1-11) were investigated for their aromatase inhibitory activities. 1,4-Naphthoquinones 1 and 4 were found to be the most potent compounds affording IC50 values 5.2 times lower than the reference drug, ketoconazole. A quantitative structure-activity relationship (QSAR) model provided good predictive performance (R2CV = 0.9783 a...

A new group of 4-(Imidazolylmethyl) quinoline derivatives possessing a methylsulfonyl COX-2 pharmacophore at the para position of the C-2 phenyl ring were designed and synthesized as selective COX-2 inhibitors and in-vitro anti breast cancer agents. In-vitro COX-1 and COX-2 inhibition studies showed that all the compounds were potent and selective inhibitors of the COX-2 isozyme with IC50 value...

The synthesis and biological evaluation of a series of novel Dual Aromatase-Sulfatase Inhibitors (DASIs) are described. It is postulated that dual inhibition of the aromatase and steroid sulfatase enzymes, both responsible for the biosynthesis of oestrogens, will be beneficial in the treatment of hormone-dependent breast cancer. The compounds are based upon the Anastrozole aromatase inhibitor t...

Previous work has shown that androgens inhibit breast cancer cells and tumor growth. On the other hand, androgens can be converted to mitogenic estrogens by aromatase in breast cancer cells. Here, we report that androgens, such as the aromatizable androstenedione and the non-aromatizable 5alpha-dihydrotestosterone, inhibit MCF-7 cell proliferation. This effect is observed only in the absence or...

Anti-Mullerian hormone (AMH) is mainly involved in the regression of Mullerian ducts in male fetuses, but it may have other functions linked to gonadal development. The present study examines the effect of AMH on steroidogenesis by Sertoli and Leydig cells in fetal and immature rats during the period where AMH is physiologically produced in the testis. The basal aromatase activity of Sertoli ce...

This study investigated the quantitative structure-activity relationship (QSAR) of imidazole derivatives of 4,7-disubstituted coumarins as inhibitors of aromatase, a potential therapeutic protein target for the treatment of breast cancer. Herein, a series of 3,7- and 4,7-disubstituted coumarin derivatives (1-34) with R1 and R2 substituents bearing aromatase inhibitory activity were modeled as a...

Neurosteroids are involved in the regulation of multiple behavioral and physiological processes metabolic activities vertebrate brain. However, central mechanisms how neurosteroid synthesis is regulated far to be understood. Gonadotropin-inhibitory hormone (GNIH) a hypothalamic neuropeptide that negatively regulates gonadotropin secretion but also inhibits sexual aggressive behaviors birds mamm...