145-13-1Relevant articles and documents
Furuya et al.
, p. 1013,1015, 1016 (1971)
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.
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.
Yamauchi et al.
, p. 3345,3346,3347 (1972)
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.
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
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Fieser,Huang-Minlon
, p. 1840,1842 (1949)
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Arcos,Lieberman
, p. 2032,2036 (1967)
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Butenandt,Fleischer
, p. 96,100 (1937)
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Microbial hydroxylation of pregnenolone derivatives
Choudhary, Muhammad Iqbal,Batool, Iffat,Shah, Syed Adnan Ali,Nawaz, Sarfraz Ahmad,Atta-ur-Rahman
, p. 1455 - 1459 (2005)
Pregnenolone (1) and pregnenolone acetate (2) were incubated with the fungi Cunninghamella elegans, Rhizopus stolonifer and Gibberella fujikuroi. Incubation of 1 with C. elegans yielded metabolites, 3 β,7 β,11 α-trihydroxypreg-5-en-20-one (3), 3 β,6 α,11 α,12 β,15 β-pentahydroxypreg-4-en-20-one (4) and 3 β,6 β,11 α-trihydroxypreg-4-en-20-one (5), while incubation with G. fujikuroi yielded two known metabolites, 3 β,7 β-dihydroxypregn-5-en-20-one (6) and 6 β,15 β-dihydroxypreg-4-ene-3,20-dione (7). Metabolites 4 and 5 were found to be new. Fermentation of 2 by C. elegans yielded four known oxidative metabolites, 1, androsta-1,4-diene-3,17-dione (8), 6 β,15 β-dihydroxyandrost-4-ene-3,17-dione (9) and 11 α,15 β-dihydroxypreg-4-ene-3,20-dione (10). Fermentation of 2 with R. stolonifer yielded two known metabolites, 11 α-hydroxypreg-4-ene-3,20-dione (11) and 7. Compounds 1-11 were screened for their cholinesterase inhibitory activity in a mechanism-based assay.
Mukherjee,D.,Engel,C.R.
, p. 597 - 604 (1979)
Stereoselective synthesis of (22R,23R,24S)-3β-Hydroxy-5-ene-22,23-dihydroxy-24-methyl-cholestane: A Brassinolide Intermediate from 16-Dehydropregnenolone Acetate
Hazra, Braja G.,Joshi, Padmakar L.,Bahule, Bharat B.,Argade, Narshinha P.,Pore, Vandana S.,Chordia, Mahendra D.
, p. 2523 - 2532 (1994)
A new synthesis of the important aldehyde 1 from easily available 16-Dehydropregnenolone acetate (16-DPA) in high yield is described.The aldehyde 1 is converted to triol 24, involving a stereoselective generation of all the four chiral centers in the brassinolide side chain.The important features of this synthesis is stereospecific generation of the acetate 14 through ene reaction using three different catalysts as well as regioselective wittig reaction on the acetoxy aldehyde 20.Conversion of triol 24 to brassinolide is known, hence this constitutes a formal total synthesis of brassinolide.
ENABLING CHOLESTEROL CATABOLISM IN HUMAN CELLS
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Paragraph 0029, (2020/07/05)
Compositions, methods, and systems for modifying sterol metabolism in a subject is disclosed. In some embodiments, the subjects may be administered one or more mammalian cells modified to express at least one sterol degrading enzyme derived from a bacterium. In many embodiments, the cell is a macrophage or monocyte stably expressing three or more enzymes that aid in opening the β ring of cholesterol. The disclosed compositions and methods may be useful in lowering cholesterol levels in a subject in need thereof. In some embodiments, the subject may have a genetic predisposition to atherosclerosis.
