72-23-1Relevant articles and documents
Structure-dependent inhibition of human and rat 11β-hydroxysteroid dehydrogenase 2 activities by phthalates
Zhao, Binghai,Chu, Yanhui,Huang, Yadong,Hardy, Dianne O.,Lin, Shaoqiang,Ge, Ren-Shan
, p. 79 - 84 (2010)
Phthalates are diesters of phthalic acid and an alcohol moiety. Phthalates have been classified as endocrine disruptors and have a broad range of effects with unknown mechanisms. Some of the effects of phthalate are consistent with disruptions of normal glucocorticoid homeostasis, and in particular, with defective function of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2). In the present study, we tested 12 phthalate diesters and four monoesters for the inhibition of human and rat kidney 11β-HSD2. We examined the modes of inhibition and looked for a relationship between the potency for inhibition and the chemical structures. Of the phthalate diesters we tested, dipropyl phthalate (DPrP) and di-n-butyl phthalate (DBP) significantly inhibited both human and rat 11β-HSD2 activities. The IC50s were 85.59 μM for DPrP and 13.69 μM for DBP when calculated for rat 11β-HSD2. As diesters, 8 of the phthalates did not affect 11β-HSD2 enzyme activity. Compared to the diesters that were inhibitory, the 8 non-inhibitory phthalates, had either fewer carbons, that is 1 or 2 carbons in the alcohol moiety, or more carbons, 5-10, as a branched or unbranched chain in the alcohol moeity. However, phthalates could be inhibitors with six carbons in the alcohol moiety if the carbons were cyclized, as in dicyclohexyl phthalate (DCHP), which inhibited rat 11β-HSD2 with an IC50 of 32.64 μM. Thus, whether a phthalate is an inhibitor may reflect the size and shape of the compound. Although the diesters are the compounds used in manufacturing and present as environmental contaminants, it is the monoester metabolites that are detected in human serum and urine. We showed that mono (2-ethylhexyl) phthalate (MEHP) significantly inhibited human (IC50 = 110.8 ± 10.9) and rat (121.8 ± 8.5 μM) 11β-HSD2 activity even though its parent compound, di(2-ethylhexyl) phthalate (DEHP) did not. MEHP was a competitive inhibitor of 11β-HSD2 enzymatic activity. We conclude that phthalates of a certain size act as competitive inhibitors.
Efficient C-21 Deoxygenation of 21-Alkoxy-20-keto Corticoid Steroids with Trimethylsilyl Iodide in the Presence of Methanol
Nagaoka, Masao,Kunitama, Yurie,Numazawa, Mitsuteru
, p. 334 - 338 (2007/10/02)
Reaction of 21-alkyl ethers 1, 4-6, 8, and 9 with a large excess of trimethylsilyl iodide (TMSI) produced the deoxygenated products 3 and 11 in low to moderate yields along with a small amount of 21-alcohols 2 and 10.The deoxygenation reaction in the presence of 1.5 molar equiv of MeOH gave the products in much higher yields than those without MeOH, except the reaction of the ethyl and n-propyl ethers 4 and 5.Treatment of 1 and 8 with trimethylsilyl chloride/NaI in the presence of MeOH gave similar results to those with TMSI.Compound 3 was also produced in high yields by reaction of 1 and 4 with HI under mild conditions.On the other hand, treatment of 17α-ketol 7 with TMSI in the presence of MeOH yielded 17aβ-methyl D-homo steroid 15.The results along with deuterium-labeling experiments with MeOD and IR and 1H NMR spectral analysis during the reaction with TMSI suggest that dealkylation of the 21-alkyl ethers precedes the deoxygenation, in which HI produced in situ by reaction of MeOH with TMSI would be involved.
Synthetic transformation using iodotrimethylsilane: Regiospecific deoxygenation of the dihydroxyacetone moiety at C-17 of corticoid steroids
Numazawa,Nagaoka,Kunitama
, p. 31 - 32 (2007/10/02)
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