183209-70-3Relevant articles and documents
Structure-activity relationships for inhibition of human 5α-reductases by polyphenols
Hiipakka, Richard A.,Zhang, Han-Zhong,Dai, Wei,Dai, Qing,Liao, Shutsung
, p. 1165 - 1176 (2002)
The enzyme steroid 5α-reductase (EC 1.3.99.5) catalyzes the NADPH-dependent reduction of the double bond of a variety of 3-oxo-Δ4 steroids including the conversion of testosterone to 5α-dihydrotestosterone. In humans, 5α-reductase activity is critical for certain aspects of male sexual differentiation, and may be involved in the development of benign prostatic hyperplasia, alopecia, hirsutism, and prostate cancer. Certain natural products contain components that are inhibitors of 5α-reductase, such as the green tea catechin (-)-epigallocatechin gallate (EGCG). EGCG shows potent inhibition in cell-free but not in whole-cell assays of 5α-reductase. Replacement of the gallate ester in EGCG with long-chain fatty acids produced potent 5α-reductase inhibitors that were active in both cell-free and whole-cell assay systems. Other flavonoids that were potent inhibitors of the type 1 5α-reductase include myricetin, quercitin, baicalein, and fisetin. Biochanin A, daidzein, genistein, and kaempferol were much better inhibitors of the type 2 than the type 1 isozyme. Several other natural and synthetic polyphenolic compounds were more effective inhibitors of the type 1 than the type 2 isozyme, including alizarin, anthrarobin, gossypol, nordihydroguaiaretic acid, caffeic acid phenethyl ester, and octyl and dodecyl gallates. The presence of a catechol group was characteristic of almost all inhibitors that showed selectivity for the type 1 isozyme of 5α-reductase. Since some of these compounds are consumed as part of the normal diet or in supplements, they have the potential to inhibit 5α-reductase activity, which may be useful for the prevention or treatment of androgen-dependent disorders. However, these compounds also may adversely affect male sexual differentiation.
Molecular Mechanism by Which Tea Catechins Decrease the Micellar Solubility of Cholesterol
Sakakibara, Takumi,Sawada, Yoshiharu,Wang, Jilite,Nagaoka, Satoshi,Yanase, Emiko
, (2019/07/03)
Tea polyphenols lower the levels of cholesterol in the blood by decreasing the cholesterol micellar solubility. To clarify this mechanism, the interactions between taurocholic acid and (-)-epigallocatechin gallate (EGCg) and its derivatives were investigated. 13C NMR studies revealed remarkable chemical-shift changes for the carbonyl carbon atom and the 1″- and 4″-positions in the galloyl moiety. Furthermore, 1H NMR studies using (-)-EGCg derivatives showed that the number of hydroxyl groups on the B ring did not affect these interactions, whereas the carbonyl carbon atom and the aromatic ring of the galloyl moiety had remarkable effects. The configuration at the 2- and 3-positions of the catechin also influenced these interactions, with the trans-configuration resulting in stronger inhibition activity than the cis-configuration. Additionally, a 1:1 component ratio for the catechin-taurocholic acid complex was determined by electrospray ionization-mass spectrometry. These molecular mechanisms contribute to the development of cholesterol-absorption inhibitors.
Synthesis and structure-activity relationship of 3-O-acylated (-)-epigallocatechins as 5α-reductase inhibitors
Lin, Shu Fu,Lin, Yu-Hsiang,Lin, Mengju,Kao, Yi-Feng,Wang, Ru-Wen,Teng, Li-Wei,Chuang, Shih-Hsien,Chang, Jia-Ming,Yuan, Ta-Tung,Fu, Kuo Chu,Huang, Kuan Pin,Lee, Ying-Shuen,Chiang, Chao-Cheng,Yang, Sheng-Chuan,Lai, Chun-Liang,Liao, Chu-Bin,Chen, Paonien,Lin, Young-Sun,Lai, Kuei-Tai,Huang, Hung-Jyun,Yang, Ju-Ying,Liu, Chia-Wei,Wei, Win-Yin,Chen, Chi-Kuan,Hiipakka, Richard A.,Liao, Shutsung,Huang, Jiann-Jyh
experimental part, p. 6068 - 6076 (2011/01/13)
A series of 3-O-acylated (-)-epigallocatechins were synthesized and their inhibition of steroid 5α-reductase was studied. They were prepared from the reaction of EGCG with tert-butyldimethylsilyl chloride followed by reductive cleavage of the ester bond. The resultant (-)-epigallocatechins penta-O-tert-butyldimethylsilyl ether was esterified with different fatty acids then desilylated to provide the corresponding products. The activity of 3-O-acylated (-)-epigallocatechins increased with the increasing carbon numbers of the fatty acid moiety, reaching maximum for 16 carbon atoms (compound 4h) with an IC50 of 0.53 μM, which was ～12-fold more potent than EGCG (IC50 = 6.29 μM). Introduction of monounsaturated fatty acid provided the most potent compound 6 (IC50 = 0.48 μM), which showed moderate anti-tumor activity in vivo.
