81811-27-0Relevant articles and documents
Ozone exposure in vivo and formation of biologically active oxysterols in the lung
Pulfer, Melissa K.,Taube, Christian,Gelfand, Erwin,Murphy, Robert C.
, p. 256 - 264 (2005)
Ozone toxicity in the lung is thought to be mediated by products derived from the reaction of ozone with components of the lung epithelial lining fluid. Cholesterol is an abundant component of this epithelial lining fluid, and it is susceptible to ozonolysis, yielding several stable products including 3β-hydroxy-5-oxo-5,6-secocholestan-6-al and 5β,6β- epoxycholesterol. Both 5β,6β-epoxycholesterol and its metabolite, cholestan-6-oxo-3,5-diol, have been shown to cause cytotoxicity in vitro, suggesting that they may be potential mediators of ozone toxicity in vivo. An ozone-sensitive mouse strain, C57BL/6J, was exposed to varying concentrations of ozone (0.5-3.0 ppm), and subsequently the levels of these cholesterol ozonolysis products were quantitated by electrospray ionization mass spectrometry in bronchoalveolar lavage fluid, lavaged cells, and lung homogenate. An ozone dose-dependent formation of these biologically active oxysterols was observed in vivo, supporting a role for these compounds in ozone toxicity. Since the 5β,6β-epoxycholesterol metabolite, cholestan-6-oxo-3,5-diol, was isobaric with other cholesterol ozonolysis products, 3β-hydroxy-5-oxo-5,6-secocholestan-6-al and its aldol condensation product, 3β-hydroxy-5β-hydroxy-B-norcholestan-6β- carboxaldehyde, detailed mass spectral analysis using electron impact ionization was utilized to differentiate these isobaric cholesterol ozonolysis products. The specific detection of cholestan-6-oxo-3,5-diol in lung homogenate after ozone exposure established formation of 5β,6β-epoxycholesterol within the lung after exposure to 0.5 ppm ozone.
Orostanal, a novel abeo-sterol inducing apoptosis in leukemia cell from a marine sponge, Stelletta hiwasaensis
Miyamoto, Tomofumi,Kodama, Kota,Aramaki, Yuko,Higuchi, Ryuichi,Van Soest, Rob W.M
, p. 6349 - 6351 (2001)
A sterol derivative, orostanal, was obtained from a marine sponge of Stelletta hiwasaensis. Spectroscopic analysis and synthetic study revealed its structure as a novel 5(6→7)abeo-sterol. Orostanal and its synthetic analog induce apoptosis in human acute promyelotic leukemia cell.
Cholesterol secosterol adduction inhibits the misfolding of a mutant prion protein fragment that induces neurodegeneration
Scheinost, Johanna C.,Witter, Daniel P.,Boldt, Grant E.,Offer, John,Wentworth Jr., Paul
, p. 9469 - 9472 (2009)
Aldehyde is critical: Atheronal-B, a cholesterol secosterol aldehyde (see structure), completely inhibits the misfolding of a prion protein fragment from its α to β form through a mechanism that involves adduction to the protein. This result offers a fresh view of lipid aldehyde-induced protein misfolding and provides a promising molecular scaffold on which to develop potential prion disease therapeutics.
Synthesis and antiproliferative activity of novel A-homo-B-norsteroid thiadiazole derivatives
Huang, Yanmin,Yang, Chunhui,Zhan, Junyan,Gan, Chunfang,Liu, Zhiping,Pang, Chunling,Chen, Haifeng,Cui, Jianguo
, p. 2952 - 2954 (2017)
Using cholesterol as a starting material, two novel steroidal thiadiazole derivatives possessing a structure of A-homo lactam and a B-nor steroidal skeleton were designed and synthesized by six steps of reactions, and their antiproliferative activities were assayed against various cancer cell lines. The result shows that compound 7b displays an excellent selective inhibition to A-549 (human lung carcinoma) cancer cell lines with an IC50 value of 8.0?μM.
Synthesis and in vitro antiproliferative evaluation of some B-norcholesteryl benzimidazole and benzothiazole derivatives
Cui, Jianguo,Qi, Binbin,Gan, Chunfang,Liu, Zhipin,Huang, Hu,Lin, Qifu,Zhao, Dandan,Huang, Yanmin
, p. 2488 - 2504 (2015)
Taking orostanal (a compound from a Japanese marine sponge, Stelletta hiwasaensis) as a lead compound, some novel B-norcholesteryl benzimidazole and benzothiazole derivatives were synthesized. The antiproliferative activity of the compounds against human cervical carcinoma (HeLa), human lung carcinoma (A549), human liver carcinoma cells (HEPG2) and normal kidney epithelial cells (HEK293T) was assayed. The results revealed that the benzimidazole group was a better substituent than benzothiazole group for increasing the antiproliferative activity of compounds. 2-(3β′-Acetoxy-5β′- hydroxy-6′-B-norcholesteryl)benzimidazole (9b) with the structure of 6 with the structure of 6 with the structure of 6 with the structure of 6 with the structure of 6 with the structure of 6 with the structure of 6 with the structure of 6 with the structure of 6with the structure of 6-benzimidazole benzimidazole benzimidazole benzimidazole benzimidazole benzimidazole displays the best displays the best displays the best displays the best displays the best displays the best displays the best antiproliferative activity to the cancer cells in all compounds, but is almost inactive to normal kidney epithelial cells (HEK293T). The assay of compound 9b to cancer cell apoptosis by flow cytometry showed that the compound was able to effectively induce cancer cell apoptosis. The research provided a theoretical reference for the exploration of new anti-cancer agents and may be useful for the design of novel chemotherapeutic drugs.
The ozonation of cholesterol: Separation and identification of 2,4-dinitrophenulhydrazine derivatization products of 3β-hydroxy-5-oxo-5,6-secocholestan-6-al
Wang, Keyang,Bermudez, Eliezer,Pryor, William A.
, p. 225 - 229 (1993)
The ozonation products of cholesterol, which are of interest as possible biomarkers of O3 exposure, were studies by derivation with 2,4-dinitrophenylhydrazine (DNPH). The DNPH derivatization of 3&x03B2;-hydroxy-5-oxo-5,6-secocholesterol-6-al (2) produces the expected trans (3b) and cis (3c) derivatives of 3x03B2;-hydroxy-5-oxo-5,6-secocholestan-6-al,a nd the unexpected DNPH derivatives of 3,5-hydroxy-B-norcholestane-6-carboxyaldehyde (3a). The structures of 3a, 3b, and 3c were identified with 1H nuclear magnetic resonance (NMR), 13C NMR, DEPT, COSY,a nd H-C correlation two-dimensional NMR techniques, and by comparison with the spectra of known compounds. A possible involving an enamine #s#x00A3;3af functionality is proposed for the formation of 3a. The ratio of sed3a/3b + 3c depends on the concentration of acid used and the reaction tiome. (Steroids 58: 225-229, 7993).
Synthesis and antiproliferative evaluation of novel steroid-benzisoselenazolone hybrids
Cui, Jianguo,Wei, Meizhen,Pang, Liping,Gan, Chunfang,Xiao, Junan,Shi, Haixin,Zhan, Junyan,Liu, Zhiping,Huang, Yanmin
, (2019/10/04)
The two different types of steroidal benzisoselenazolone hybrids were synthesized by incorporating benzisoselenazolone scaffold into dehydroepiandrosterone and B-norcholesterol. The antiproliferative activity of the synthesized compounds against some carcinoma cell lines were investigated. The results showed that some of these compounds have better inhibitory activity than abiraterone on the proliferation of tumor cells associated with human growth hormone, and have less cytotoxicity on normal human cells. In particular, the IC50 values of the compound 8a and 8f are 5.4 and 6.5 μmol/L against human ovarian carcinoma (SKOV3) cell line, and possess SI values of 13.9 and 10.5, respectively. The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs.
Gonanes B-reducing a benzimidazole compound and its preparation and use
-
Paragraph 0055; 0058, (2017/01/12)
The invention provides a B-norcholestane benzimidazole compound as well as a preparation method and application thereof. The general structural formula of the compound is as shown in the specification, wherein R refers to any one of H or COCH3; R1 refers to F, NO2, CF3, H, CH3 or OCH3; and R2 refers to H or CH3. The B-norcholestane benzimidazole compound disclosed by the invention has high inhibitory activity on human cervical carcinoma cell lines, human lung carcinoma cell lines and human liver cancer cells. The B-norcholestane benzimidazole compound disclosed by the invention is low in toxicity and low in injury of normal cells, has an effective effect of inhibiting the cancer cells during low concentration, basically does not cause drug injury to normal cells and can be applied to preparing medicines for treating the cancers.
Highly sensitive fluorescent method for the detection of cholesterol aldehydes formed by ozone and singlet molecular oxygen
Mansano, Fernando V.,Kazaoka, Rafaella M. A.,Ronsein, Graziella E.,Prado, Fernanda M.,Genaro-Mattos, Thiago C.,Uemi, Miriam,Mascio, Paolo Di,Miyamoto, Sayuri
experimental part, p. 6775 - 6781 (2011/04/25)
Cholesterol oxidation gives rise to a mixture of oxidized products. Different types of products are generated according to the reactive species being involved. Recently, attention has been focused on two cholesterol aldehydes, 3β-hydroxy-5β-hydroxy-B-norcholestane-6β- carboxyaldehyde (1a) and 3β-hydroxy-5-oxo-5,6-secocholestan-6-al (1b). These aldehydes can be generated by ozone-, as well as by singlet molecular oxygen-mediated cholesterol oxidation. It has been suggested that 1b is preferentially formed by ozone and 1a is preferentially formed by singlet molecular oxygen. In this study we describe the use of 1-pyrenebutyric hydrazine (PBH) as a fluorescent probe for the detection of cholesterol aldehydes. The formation of the fluorescent adduct between 1a with PBH was confirmed by HPLC-MS/MS. The fluorescence spectra of PBH did not change upon binding to the aldehyde. Moreover, the derivatization was also effective in the absence of an acidified medium, which is critical to avoid the formation of cholesterol aldehydes through Hock cleavage of 5α-hydroperoxycholesterol. In conclusion, PBH can be used as an efficient fluorescent probe for the detection/quantification of cholesterol aldehydes in biological samples. Its analysis by HPLC coupled to a fluorescent detector provides a sensitive and specific way to quantify cholesterol aldehydes in the low femtomol range.
The ratio of cholesterol 5,6-secosterols formed from ozone and singlet oxygen offers insight into the oxidation of cholesterol in vivo
Wentworth, Anita D.,Song, Byeong-Doo,Nieva, Jorge,Shafton, Asher,Tripurenani, Sangeetha,Wentworth Jr., Paul
supporting information; experimental part, p. 3098 - 3100 (2009/12/01)
Ongoing efforts to unravel the origins of the cholesterol 5,6-secosterols (1a and 1b) in biological systems have revealed that the two known chemical routes to these oxysterols, ozonolysis of cholesterol (3) and Hock-cleavage of 5-α-hydroperoxycholesterol (4a), are distinguishable based upon the ratio of the hydrazone derivatives (2a and 2b) formed in each case and this ratio offers an insight into the chemical origin of the secosterols in vivo. The Royal Society of Chemistry 2009.
