145-13-1Relevant articles and documents
Synthesis and Biological Evaluation of Vitamin D3 Metabolite 20S,23S-Dihydroxyvitamin D3 and Its 23R Epimer
Lin, Zongtao,Marepally, Srinivasa R.,Ma, Dejian,Kim, Tae-Kang,Oak, Allen Sw.,Myers, Linda K.,Tuckey, Robert C.,Slominski, Andrzej T.,Miller, Duane D.,Li, Wei
, p. 5102 - 5108 (2016)
The vitamin D3 metabolite, 20S,23S-dihydroxyvitamin D3, was chemically synthesized for the first time and identified to be the same as the enzymatically produced metabolite. The C23 absolute configurations of both 20S,23S/R-dihydroxyvitamin D3 epimers were unambiguously assigned by NMR and Mosher ester analysis. Their kinetics of CYP27B1 metabolism were investigated during the production of their 1α-hydroxylated derivatives. Bioactivities of these products were compared in terms of vitamin D3 receptor activation, anti-inflammatory, and antiproliferative activities.
Enzymatic deacetylation of steroids bearing labile functions
Baldessari, Alicia,Maier, Marta S.,Gros, Eduardo G.
, p. 4349 - 4352 (1995)
Lipase from Candida cylindracea and Candida antarctica catalyzes the removal of acetyl groups from 3β-acetoxypregn-5-en-20-one and 3β-acetoxy-20-(S)-hydroxycholest-5-en-23-one through a transesterification reaction in organic solvents.
1,5-Hydride shift in Wolff-Kishner reduction of (20R)-3β,20, 26-trihydroxy-27-norcholest-5-en-22-one: Synthetic, quantum chemical, and NMR studies
Szendi, Zsuzsanna,Forgo, Peter,Tasi, Gyula,Boecskei, Zsolt,Nyerges, Levente,Sweet, Frederick
, p. 31 - 38 (2002)
Heating (20R)-3β,20,26-trihydroxy-27-norcholest-5-en-22-one (1) with hydrazine and KOH at 160°C completely converted the steroid to a diastereoisomeric mixture of the new (20R,22RS)-27-norcholest-5-ene-3β,20,22-triols (2). Exclusive formation of 2 suggest
Ile351, Leu355 and Ile461 residues are essential for catalytic activity of bovine cytochrome P450scc (CYP11A1)
Glyakina, Anna V.,Strizhov, Nicolai I.,Karpov, Mikhail V.,Dovidchenko, Nikita V.,Matkarimov, Bakhyt T.,Isaeva, Ludmila V.,Efimova, Vera S.,Rubtsov, Mikhail A.,Novikova, Ludmila A.,Donova, Marina V.,Galzitskaya, Oxana V.
, p. 80 - 90 (2019)
Cytochrome P450scc (CYP11A1) is a mammalian mitochondrial enzyme which catalyzes cholesterol side chain cleavage to form pregnenolone. Along with cholesterol, some other steroids including sterols with a branched side chain like β-sitosterol are the substrates for the enzyme, but the activity towards β-sitosterol is rather low. Modification of the catalytic site conformation could provide more effective β-sitosterol bioconversion by the enzyme. This study was aimed to find out the amino acid residues substitution of which could modify the conformation of the active site providing possible higher enzyme activity towards β-sitosterol. After structural and bioinformatics analysis three amino acid residues I351, L355, I461 were chosen. Molecular dynamics simulations of P450scc evidenced the stability of the wild type, double (I351A/L355A) and triple (I351A/L355A/I461A) mutants. Mutant variants of cDNA encoding P450scc with the single, double and triple mutations were obtained by site-directed mutagenesis. However, the experimental data indicate that the introduced single mutations Ile351A, Leu355A and Ile461A dramatically decrease the target catalytic activity of CYP11A1, and no activity was observed for double and triple mutants obtained. Therefore, isoleucine residues 351 and 461, and leucine residue 355 are important for the cytochrome P450scc functioning towards sterols both with unbranched (cholesterol) and branched (sitosterol) side chains.
Discovery of novel steroidal-chalcone hybrids with potent and selective activity against triple-negative breast cancer
Bai, Chengfeng,Hou, Qiangqiang,Lin, Xin,Lu, Xiang,Luo, Guoshun,Wei, Hanlin,Xiang, Hua
, (2020)
A series of novel steroidal-chalcone derivates were designed and synthesized based on the molecular hybridization strategy and further evaluated for their growth inhibitory activity against three human cancer cell lines. The MTT results indicated that most compounds were apparently more sensitive to human breast cancer cells MDA-MB-231. Compounds 8 and 18 exerted the best cytotoxic activity against triple-negative MDA-MB-231 cells with the IC50 values of 0.42 μM and 0.52 μM respectively, which were 23-fold increase or more compared with 5-Fu. Further mechanism studies demonstrated that compound 8 could induce cells apoptosis through regulating Bcl-2/Bax proteins and activating caspase-3 signaling pathway. Moreover, compound 8 could upregulate the cellular ROS levels which accelerated the apoptosis of MDA-MB-231 cells. In addition, interestingly, cell cycle assay showed that compound 8 could arrest MDA-MB-231 cells at S phase but not commonly anticipated G2/M phase. These evidences fully confirmed that compound 8 could be a potential candidate that deserves further development as an antitumor agent against triple-negative breast cancer.
A new mild PTSA-catalyzed method for sulfate ester hydrolysis and acid-catalyzed rearrangement of 12-acetyl-diene-11-ol tetracyclic triterpenoids involving an angular methyl migration
Singh
, p. 6973 - 6976 (2000)
Tetracyclic triterpenoids containing the 12-acetyl-Δ8,14-diene-ll-ol moiety undergo a series of acid-catalyzed rearrangements. The rearrangement products have been characterized, plausible mechanisms for the rearrangement have been elucidated and conditions have been developed to give high yields of the rearrangement products. A new and general PTSA·H2O and PPTS-catalyzed sulfate hydrolysis method has been developed. (C) 2000 Elsevier Science Ltd.
Inhibition of bovine adrenocortical cytochrome P-450scc by 3,3'-dimethoxybenzidine
Duval,Vickery
, p. 91 - 101 (1981)
The effect of 3,3'-dimethoxybenzidine (o-dianisidine) on the conversion of cholesterol to pregnenolone was investigated in a reconstituted side chain cleavage system using enzymes purified from bovine adrenal cortex; d-p-aminoglutethimide was also assayed under similar conditions for comparison. 3,3'-Dimethoxybenzidine was found to be a potent inhibitor of pregnenolone formation, causing 50% inhibition at a concentration of 1.5 μM when using 70 μM cholesterol - this does is approximately one fourth that required of 3-methoxybenzidine and one twentieth that required of benzidine for equal inhibition. In the same system, d-p-aminoglutethimide exhibited an I50 value of about 55 μM. No effects of 3,3'-dimethoxybenzidine on adrenodoxin reductase or adrenodoxin activities could be detected, and inhibition of side chain cleavage could be relieved by dilution suggesting that the inhibitor acts by reversibly binding to cytochrome P-450 scc.
Mild deprotection of steroid esters by bis(tributyltin)oxide
Perez, Marina G.,Maier, Marta S.
, p. 3311 - 3314 (1995)
Bis(tributyltin)oxide (BBTO) has been utilized for the first time for the deprotection of steroid esters. The best results were obtained for 3β-esters, in particular the selective hydrolysis of the 3β-acetyl group in 3β,6α-diacetoxy-5α-pregnan-20-one to give 6α-acetoxy-3β-hydroxy-5α-pregnan-20-one.
Human placental cholesterol side-chain cleavage: enzymatic synthesis of (22R)-20α,22-dihydroxycholesterol
Tuckey, Robert C.,Cameron, Kathryn J.
, p. 230 - 233 (1993)
(22R)-20α,22-Dihydroxycholesterol is the second intermediate in the conversion of cholesterol to pregnenolone by cytochrome P450scc in steroidogenic tissues.We report a rapid method for the enzymatic synthesis of (22R)-20α,22-dihydroxycholesterol from (22R)-20-hydroxycholesterol using mitochondria from the human placenta. (Steroids 58:230-233, 1993) Keywords: steroids; cytochrome P450scc; placental mitochondria; (22R)-20α,22-dihydroxycholesterol; (22R)-22-hydroxycholesterol; pregnenolone
Proline-promoted dehydroxylation of α-ketols
Mostinski, Yelena,Lankri, David,Konovalov, Yana,Nataf, Riva,Tsvelikhovsky, Dmitry
, p. 9345 - 9350 (2019)
A new single-step proline-potassium acetate promoted reductive dehydroxylation of α-ketols is reported. We introduce the unexplored reactivity of proline and, for the first time, reveal its ability to function as a reducing agent. The developed metal-free and open-flask operation generally results in good yields. Our protocol allows the challenging selective dehydroxylation of hydroxyketones without affecting other functional groups.
