ABSTRACT
Estrogen receptors (ERs) are members of nuclear receptors and related to several diseases such as cancer, inflammation and osteoporosis. ERs have two forms, ERα and ERβ, which have different functions and organism distributions. Compounds selectively targeting ERβ can regulate important physiological functions and avoid the side effects caused by targeting ERα. Therefore, selective ERβ ligands have received considerable research interest in recent years. In this article, different kinds of selective ERβ ligands were summarized and their structure-activity relationships were also analyzed.
Subject(s)
Humans , Estrogen Receptor beta , Chemistry , Ligands , Structure-Activity RelationshipABSTRACT
Aromatase is a key enzyme responsible for in vivo estrogen biosynthesis. Inhibition of the activity of the aromatase has become an alterative way for treatment of breast cancer. In this review, the structure and catalytic mechanism of the aromatase is briefly introduced followed by thorough review of the progress in the study of the steroidal and non-steroidal aromatase inhibitors. This review is focused on the natural compounds that exhibit the aromatase inhibition, which include flavonoids, xanthones, coumarins, and sesquiterpenes. The structure-activity relationship of these compounds is also discussed.
Subject(s)
Humans , Androstenedione , Antineoplastic Agents , Chemistry , Pharmacology , Therapeutic Uses , Aromatase , Chemistry , Metabolism , Pharmacology , Aromatase Inhibitors , Chemistry , Classification , Pharmacology , Therapeutic Uses , Breast Neoplasms , Drug Therapy , Catalysis , Coumarins , Chemistry , Pharmacology , Estrogens , Flavonoids , Chemistry , Pharmacology , Inhibitory Concentration 50 , Nitriles , Chemistry , Pharmacology , Sesquiterpenes , Chemistry , Pharmacology , Structure-Activity Relationship , Triazoles , Chemistry , Pharmacology , Xanthones , Chemistry , PharmacologyABSTRACT
Farnesoid X receptor (FXR) belongs to the nuclear receptor superfamily. It is highly related to the formation of metabolic syndrome and the glucose homeostasis, and therefore represents an important drug target against metabolic diseases and diabetes. In recent years, great progress has been made in the agonists, antagonists, and crystal structures of FXR. The diverse FXR ligands and their structure-activity relationship are reviewed in this article. The advances in the crystal structures of FXR in complex with different ligands are also introduced.
Subject(s)
Animals , Humans , Anticholesteremic Agents , Chemistry , Pharmacology , Azepines , Chemistry , Pharmacology , Benzene Derivatives , Chemistry , Pharmacology , Chenodeoxycholic Acid , Chemistry , Pharmacology , Crystallization , Indoles , Chemistry , Pharmacology , Isoxazoles , Chemistry , Pharmacology , Ligands , Molecular Structure , Multienzyme Complexes , Chemistry , Pharmacology , Pregnenediones , Chemistry , Pharmacology , Receptors, Cytoplasmic and Nuclear , Metabolism , Structure-Activity RelationshipABSTRACT
<p><b>OBJECTIVE</b>Environmental estrogens at an elevated concentration are known to produce adverse effects on human and animal life. However, the majority of researches have been focused on industrial discharges, while the impact of livestock wastes as a source of endocrine disrupters in aquatic environments has been rarely elucidated. In order to investigate the contribution of environmental estrogens from livestock, the estrogenic activity in water samples from a farm wastewater treatment plant was analyzed by a recombinant yeast screening method.</p><p><b>METHODS</b>The extracts prepared from 15 selected water samples from the farm wastewater treatment plant, among which 6 samples were from pre-treatment section (influents) and 9 from post-treatment section (effluents), were analyzed for estrogenic activity by cellar bioassay. Yeast cells transfected with the expression plasmid of human estrogen receptor and the Lac Z reporter plasmid encoding beta-galactossidase, were used to measure the estrogen-like compounds in the farm wastewater treatment plant.</p><p><b>RESULTS</b>The wastewater samples from influents showed a higher estrogenic potency than the effluent samples showing a low induction of beta-galactossidase relative to solvent control condition. By comparison with a standard curve for 17 beta-estradiol (E2), estrogenic potency in water samples from the influents was calculated as E2-equivalent and ranged from 0.1 to 150 pM E2-equivalent. The estrogenic potency in water samples from the effluents was significantly lower than that in the influents, and 7 water samples had less detectable limit in the total of 9 samples.</p><p><b>CONCLUSION</b>Yeast bioassay of estrogenic activity in most of the samples from the farm wastewater after disposal by traditional sewage treatment showed negative results.</p>