13027-33-3Relevant academic research and scientific papers
Targeting autophagy inhibits melanoma growth by enhancing NK cells infiltration in a CCL5-dependent manner
Mgrditchian, Takouhie,Arakelian, Tsolere,Paggetti, Jér?me,Noman, Muhammad Zaeem,Viry, Elodie,Moussay, Etienne,Van Moer, Kris,Kreis, Stephanie,Guerin, Coralie,Buart, Stephanie,Robert, Caroline,Borg, Christophe,Vielh, Philippe,Chouaib, Salem,Berchem, Guy,Janji, Bassam
, p. E9271 - E9279 (2017/11/07)
While blocking tumor growth by targeting autophagy is well established, its role on the infiltration of natural killer (NK) cells into tumors remains unknown. Here, we investigate the impact of targeting autophagy gene Beclin1 (BECN1) on the infiltration of NK cells into melanomas. We show that, in addition to inhibiting tumor growth, targeting BECN1 increased the infiltration of functional NK cells into melanoma tumors. We provide evidence that driving NK cells to the tumor bed relied on the ability of autophagy-defective tumors to transcriptionally overexpress the chemokine gene CCL5. Such infiltration and tumor regression were abrogated by silencing CCL5 in BECN1-defective tumors. Mechanistically, we show that the up-regulated expression of CCL5 occurred through the activation of its transcription factor c-Jun by a mechanism involving the impairment of phosphatase PP2A catalytic activity and the subsequent activation of JNK. Similar to BECN1, targeting other autophagy genes, such as ATG5, p62/SQSTM1, or inhibiting autophagy pharma-cologically by chloroquine, also induced the expression of CCL5 in melanoma cells. Clinically, a positive correlation between CCL5 and NK cell marker NKp46 expression was found in melanoma patients, and a high expression level of CCL5 was correlated with a significant improvement of melanoma patients’ survival. We believe that this study highlights the impact of targeting autophagy on the tumor infiltration by NK cells and its benefit as a novel therapeutic approach to improve NK-based immunotherapy.
Structure-activity relationships of oxysterol-derived pharmacological chaperones for Niemann-Pick type C1 protein
Ohgane, Kenji,Karaki, Fumika,Noguchi-Yachide, Tomomi,Dodo, Kosuke,Hashimoto, Yuichi
supporting information, p. 3480 - 3485 (2014/07/22)
Niemann-Pick disease type C is a fatal neurodegenerative disease, and its major cause is mutations in NPC1 gene. This gene encodes NPC1 protein, a late endosomal polytopic membrane protein required for intracellular cholesterol trafficking. One prevalent mutation (I1061T) has been shown to cause a folding defect, which results in failure of endosomal localization of the protein, leading to loss-of-function phenotype. We have previously demonstrated that several oxysterols and their derivatives act as pharmacological chaperones; binding of these compounds to NPC1I1061T mutant protein corrects the localization/maturation defect of the mutant protein. Here, we disclose detailed structure-activity relationships of oxysterol derivatives as pharmacological chaperones for NPC1I1061T mutant.
Synthesis and plant growth promoting activity of polyhydroxylated ketones bearing the 5α-hydroxy-6-oxo moiety and cholestane side chain
Rosado-Abón, Anielka,De Dios-Bravo, Guadalupe,Rodríguez-Sotres, Rogelio,Iglesias-Arteaga, Martín A.
experimental part, p. 461 - 466 (2012/05/19)
Three polyhydroxylated ketones bearing the 5α-hydroxy-6-oxo moiety were obtained from cholesterol. Two of them show plant growth promoting activity in the bean's second internode bioassay. The obtained results indicate that the presence of the 5α-hydroxy-
Sterols as anticancer agents: Synthesis of ring-B oxygenated steroids, cytotoxic profile, and comprehensive SAR analysis
Carvalho, Jo?o F. S.,Silva, M. Manuel Cruz,Moreira, Jo?o N.,Sim?es, Sérgio,Sá E Melo, M. Luisa
supporting information; experimental part, p. 7632 - 7638 (2011/02/21)
The cytotoxicity of oxysterols was systematically studied in tumor and normal cells. Synthetic strategies to prepare this library included oxidations at ring B and a new method to yield 6β-hemiphthalates directly from Δ5-steroids. Most oxysterols were cytotoxic and showed selectivity toward cancer cells, LAMA-84 cells (leukemia) being particularly sensitive to 4, 8, 22, and 27 (IC50 5.6 μM). The structural requirements to induce selective toxicity are discussed to shed light on the development of new anticancer drugs.
Microwave-assisted transformation of α,β- and β,γ-unsaturated nitroalkenes into carbonyl compounds
Das, Deba D.,Nayak, Amalendu,Nanda, Bhagabat,Das, Nalin B.
, p. 481 - 482 (2007/10/03)
Vinyl and allylic nitroalkenes have been converted into the corresponding carbonyl compounds in good yield using tin(II) chloride dihydrate under microwave irradiation.
Kinetic model for studying the effect of quercetin on cholesterol oxidation during heating
Chien, John-Tung,Hsu, Da-Jung,Chen, Bing-Huei
, p. 1486 - 1492 (2007/10/03)
Inhibition of the heat-induced cholesterol oxidation at 150°C by incorporation of quercetin was kinetically studied. Results showed that without quercetin, the cholesterol oxidation products (COPs) concentration increased with increasing heating time. A low amount (0.002%, w/w) of quercetin was effective in inhibiting the formation of COPs during the initial heating period (≤30 min) at 150°C. However, after prolonged heating (30-120 min), a low antioxidant activity was observed because of the degradation of quercetin. When using nonlinear regression models for kinetic study of cholesterol oxidation in the absence of quercetin, the epoxidation showed the highest rate constant (h-1 = 683.1), followed by free radical chain reaction (h -1 = 453.5), reduction (h-1 = 290.3), dehydration (h -1 = 155.5), triol dehydrogenation (h-1 = 5.35), dehydrogenation (h-1 = 0.68), thermal degradation (h-1 = 0.66), and triol formation (h-1 = 0.38). However, in the presence of quercetin, the reaction rate constants (h-1) for epoxidation (551.4), free radical chain reaction (111.7), and thermal degradation (0.28) were reduced greatly. The kinetic model developed in this study can be used to predict the inhibition of COPs by quercetin during the heating of cholesterol.
Thiazolium ylide-catalyzed intramolecular aldehyde-ketone benzoin-forming reactions: Substrate scope
Hachisu, Yoshifumi,Bode, Jeffrey W.,Suzuki, Keisuke
, p. 1097 - 1100 (2007/10/03)
The scope and limitations of intramolecular benzoin-forming reactions of aldehydes and ketones catalyzed by the combination of a thiazolium salt and a base are described. After optimization of the reaction conditions, five- and six-membered cyclic acyloins were obtained in good to excellent yields and competing reactions such as intramolecular aldol reactions were suppressed. The analogous closure of seven-membered rings proved difficult.
Kinetic studies of cholesterol oxidation as inhibited by stearylamine during heating
Chien, John-Tung,Huang, Dong-Yong,Chen, Bing-Huei
, p. 7132 - 7138 (2007/10/03)
The formation of cholesterol oxidation products (COPs) during heating in the presence of stearylamine at 140°C was analyzed by high-performance liquid chromatography (HPLC) and kinetically studied by use of nonlinear regression models. Results indicated that the COPs concentration increased with increasing heating time, and stearylamine was shown to reduce both oxidation and degradation rates of cholesterol. Without stearylamine, the highest rate constant (per hour) was observed for epoxidation (545.4), followed by free radical chain reaction (251.0), reduction (147.3), dehydration (95.8), triol dehydrogenation (4.7), degradation (0.34), triol formation (0.31), and dehydrogenation (0.13). With stearylamine, the epoxidation and free radical chain reaction rates could be reduced by about 800- and 3.4-fold, respectively, and triol formation during oxidation could be completely inhibited. In addition, the reactions for reduction, dehydration, degradation, and dehydrogenation could proceed slower in the presence of stearylamine. The kinetic model developed in this study can be used to predict the inhibition of COPs formation by stearylamine during heating of cholesterol.
Oxidation of Alcohols with o-Iodobenzoic Acid (IBX) in DMSO: A New Insight into an Old Hypervalent Iodine Reagent
Frigerio, Marco,Santagostino, Marco,Sputore, Simona,Palmisano, Giovanni
, p. 7272 - 7276 (2007/10/03)
The ultracentennial 10-I-4 iodinane oxide IBX (3; o-iodoxybenzoic acid; 1-hydroxy-1,2-benziodoxol-3(1H)-one 1-oxide) represents a new oxidizing reagent that successfully joins to the large family of known oxidants.IBX, in contrast to other valuable oxidants, is inexpensive to prepare and easy to handle, can tolerate moisture and water, and generally gives very good yields.Furthermore, IBX is mild and chemoselective (primary alcohols are converted into aldehydes with no overoxidation to acids; 1,2-diols are converted to α-ketols or α-diketones without oxidative cleavage; amino alcohols are oxidized to amino carbonyls, without protection of the amino group; sensitive heterocycles are not affected; various other functional groups are compatible with IBX oxidation).IBX is versatile (it works in various solvents and it is highly sensitive to temperature variations), and its solutions in DMSO are stable enough to carry out the oxidation reaction easily.
A Mild Oxidizing Reagent for Alcohols and 1,2-Diols: o-Iodoxybenzoic Acid (IBX) in DMSO
Frigerio, Marco,Santagostino, Marco
, p. 8019 - 8022 (2007/10/02)
o-Iodoxybenzoic acid (IBX) smoothly oxidizes primary and secondary alcohols to aldehydes and ketones, respectively. 1,2-Diols are converted to α-ketols or α-diketones without any oxidative cleavage of the glycol C-C bond.IBX oxidations are easily conducted in DMSO solution at room temperature, with yields ranging from good to quantitative.
