The Experts below are selected from a list of 5295 Experts worldwide ranked by ideXlab platform
Chin Ho Chen - One of the best experts on this subject based on the ideXlab platform.
-
Synthesis of Lithocholic Acid Derivatives as Proteasome Regulators
ACS medicinal chemistry letters, 2012Co-Authors: Zhao Dang, Kuo Hsiung Lee, Li Huang, Kathy Jung, Keduo Qian, Chin Ho ChenAbstract:Accumulation of aberrant protein aggregates, such as amyloid β peptide (Aβ), due to decreased proteasome activities, might contribute to the neurodegeneration in Alzheimer's disease. In this study, Lithocholic Acid derivatives 3α-O-pimeloyl-Lithocholic Acid methyl ester (2) and its isosteric isomer (6) were found to activate the chymotrypsin-like activity of the proteasome at an EC50 of 7.8 and 4.3 μM, respectively. Replacing the C24 methyl ester in 2 with methylamide resulted in a complete devoid of proteasome activating activity. Epimerizing the C3 substituent from an α to β orientation transformed the activator into a proteasome inhibitor. Unlike the cellular proteasome activator PA28, proteasome activated by 2 was not inhibited by Aβ. Furthermore, 2 potently antagonized the inhibitory effect of Aβ on the proteasome. In summary, compound 2 represents a novel class of small molecules that not only activates the proteasome but also antagonizes the inhibitory effect of Aβ on the proteasome.
-
Synthesis and proteasome inhibition of Lithocholic Acid derivatives
Bioorganic & medicinal chemistry letters, 2011Co-Authors: Zhao Dang, Andrew Lin, Dominique N. Soroka, Kuo Hsiung Lee, Li Huang, Chin Ho ChenAbstract:Abstract A new class of proteasome inhibitors was synthesized using Lithocholic Acid as a scaffold. Modification at the C-3 position of Lithocholic Acid with a series of Acid acyl groups yielded compounds with a range of potency on proteasome inhibition. Among them, the phenylene diacetic Acid hemiester derivative ( 13 ) displayed the most potent proteasome inhibition with IC 50 = 1.9 μM. Enzyme kinetic analysis indicates that these Lithocholic Acid derivatives are noncompetitive inhibitors of the proteasome.
Zhao Dang - One of the best experts on this subject based on the ideXlab platform.
-
Synthesis of Lithocholic Acid Derivatives as Proteasome Regulators
ACS medicinal chemistry letters, 2012Co-Authors: Zhao Dang, Kuo Hsiung Lee, Li Huang, Kathy Jung, Keduo Qian, Chin Ho ChenAbstract:Accumulation of aberrant protein aggregates, such as amyloid β peptide (Aβ), due to decreased proteasome activities, might contribute to the neurodegeneration in Alzheimer's disease. In this study, Lithocholic Acid derivatives 3α-O-pimeloyl-Lithocholic Acid methyl ester (2) and its isosteric isomer (6) were found to activate the chymotrypsin-like activity of the proteasome at an EC50 of 7.8 and 4.3 μM, respectively. Replacing the C24 methyl ester in 2 with methylamide resulted in a complete devoid of proteasome activating activity. Epimerizing the C3 substituent from an α to β orientation transformed the activator into a proteasome inhibitor. Unlike the cellular proteasome activator PA28, proteasome activated by 2 was not inhibited by Aβ. Furthermore, 2 potently antagonized the inhibitory effect of Aβ on the proteasome. In summary, compound 2 represents a novel class of small molecules that not only activates the proteasome but also antagonizes the inhibitory effect of Aβ on the proteasome.
-
Synthesis and proteasome inhibition of Lithocholic Acid derivatives
Bioorganic & medicinal chemistry letters, 2011Co-Authors: Zhao Dang, Andrew Lin, Dominique N. Soroka, Kuo Hsiung Lee, Li Huang, Chin Ho ChenAbstract:Abstract A new class of proteasome inhibitors was synthesized using Lithocholic Acid as a scaffold. Modification at the C-3 position of Lithocholic Acid with a series of Acid acyl groups yielded compounds with a range of potency on proteasome inhibition. Among them, the phenylene diacetic Acid hemiester derivative ( 13 ) displayed the most potent proteasome inhibition with IC 50 = 1.9 μM. Enzyme kinetic analysis indicates that these Lithocholic Acid derivatives are noncompetitive inhibitors of the proteasome.
Li Huang - One of the best experts on this subject based on the ideXlab platform.
-
Synthesis of Lithocholic Acid Derivatives as Proteasome Regulators
ACS medicinal chemistry letters, 2012Co-Authors: Zhao Dang, Kuo Hsiung Lee, Li Huang, Kathy Jung, Keduo Qian, Chin Ho ChenAbstract:Accumulation of aberrant protein aggregates, such as amyloid β peptide (Aβ), due to decreased proteasome activities, might contribute to the neurodegeneration in Alzheimer's disease. In this study, Lithocholic Acid derivatives 3α-O-pimeloyl-Lithocholic Acid methyl ester (2) and its isosteric isomer (6) were found to activate the chymotrypsin-like activity of the proteasome at an EC50 of 7.8 and 4.3 μM, respectively. Replacing the C24 methyl ester in 2 with methylamide resulted in a complete devoid of proteasome activating activity. Epimerizing the C3 substituent from an α to β orientation transformed the activator into a proteasome inhibitor. Unlike the cellular proteasome activator PA28, proteasome activated by 2 was not inhibited by Aβ. Furthermore, 2 potently antagonized the inhibitory effect of Aβ on the proteasome. In summary, compound 2 represents a novel class of small molecules that not only activates the proteasome but also antagonizes the inhibitory effect of Aβ on the proteasome.
-
Synthesis and proteasome inhibition of Lithocholic Acid derivatives
Bioorganic & medicinal chemistry letters, 2011Co-Authors: Zhao Dang, Andrew Lin, Dominique N. Soroka, Kuo Hsiung Lee, Li Huang, Chin Ho ChenAbstract:Abstract A new class of proteasome inhibitors was synthesized using Lithocholic Acid as a scaffold. Modification at the C-3 position of Lithocholic Acid with a series of Acid acyl groups yielded compounds with a range of potency on proteasome inhibition. Among them, the phenylene diacetic Acid hemiester derivative ( 13 ) displayed the most potent proteasome inhibition with IC 50 = 1.9 μM. Enzyme kinetic analysis indicates that these Lithocholic Acid derivatives are noncompetitive inhibitors of the proteasome.
Kuo Hsiung Lee - One of the best experts on this subject based on the ideXlab platform.
-
Synthesis of Lithocholic Acid Derivatives as Proteasome Regulators
ACS medicinal chemistry letters, 2012Co-Authors: Zhao Dang, Kuo Hsiung Lee, Li Huang, Kathy Jung, Keduo Qian, Chin Ho ChenAbstract:Accumulation of aberrant protein aggregates, such as amyloid β peptide (Aβ), due to decreased proteasome activities, might contribute to the neurodegeneration in Alzheimer's disease. In this study, Lithocholic Acid derivatives 3α-O-pimeloyl-Lithocholic Acid methyl ester (2) and its isosteric isomer (6) were found to activate the chymotrypsin-like activity of the proteasome at an EC50 of 7.8 and 4.3 μM, respectively. Replacing the C24 methyl ester in 2 with methylamide resulted in a complete devoid of proteasome activating activity. Epimerizing the C3 substituent from an α to β orientation transformed the activator into a proteasome inhibitor. Unlike the cellular proteasome activator PA28, proteasome activated by 2 was not inhibited by Aβ. Furthermore, 2 potently antagonized the inhibitory effect of Aβ on the proteasome. In summary, compound 2 represents a novel class of small molecules that not only activates the proteasome but also antagonizes the inhibitory effect of Aβ on the proteasome.
-
Synthesis and proteasome inhibition of Lithocholic Acid derivatives
Bioorganic & medicinal chemistry letters, 2011Co-Authors: Zhao Dang, Andrew Lin, Dominique N. Soroka, Kuo Hsiung Lee, Li Huang, Chin Ho ChenAbstract:Abstract A new class of proteasome inhibitors was synthesized using Lithocholic Acid as a scaffold. Modification at the C-3 position of Lithocholic Acid with a series of Acid acyl groups yielded compounds with a range of potency on proteasome inhibition. Among them, the phenylene diacetic Acid hemiester derivative ( 13 ) displayed the most potent proteasome inhibition with IC 50 = 1.9 μM. Enzyme kinetic analysis indicates that these Lithocholic Acid derivatives are noncompetitive inhibitors of the proteasome.
Alejandra Gomez-perez - One of the best experts on this subject based on the ideXlab platform.
-
Mechanisms through which Lithocholic Acid delays yeast chronological aging under caloric restriction conditions
Oncotarget, 2018Co-Authors: Anthony Arlia-ciommo, Anna Leonov, Adam Beach, Vincent R. Richard, Simon D. Bourque, Michelle T. Burstein, Alexander A. Goldberg, Pavlo Kyryakov, Karamat Mohammad, Alejandra Gomez-perezAbstract:// Anthony Arlia-Ciommo 1 , Anna Leonov 1 , Karamat Mohammad 1 , Adam Beach 1 , Vincent R. Richard 1 , Simon D. Bourque 1 , Michelle T. Burstein 1 , Alexander A. Goldberg 1 , Pavlo Kyryakov 1 , Alejandra Gomez-Perez 1 , Olivia Koupaki 1 and Vladimir I. Titorenko 1 1 Department of Biology, Concordia University, Montreal, Quebec, Canada Correspondence to: Vladimir I. Titorenko, email: vladimir.titorenko@concordia.ca Keywords: yeast; cellular aging; geroprotectors; Lithocholic Acid; metabolism Received: August 15, 2018 Accepted: September 17, 2018 Published: October 09, 2018 ABSTRACT All presently known geroprotective chemical compounds of plant and microbial origin are caloric restriction mimetics because they can mimic the beneficial lifespan- and healthspan-extending effects of caloric restriction diets without the need to limit calorie supply. We have discovered a geroprotective chemical compound of mammalian origin, a bile Acid called Lithocholic Acid, which can delay chronological aging of the budding yeast Saccharomyces cerevisiae under caloric restriction conditions. Here, we investigated mechanisms through which Lithocholic Acidcan delay chronological aging of yeast limited in calorie supply. We provide evidence that Lithocholic Acid causes a stepwise development and maintenance of an aging-delaying cellular pattern throughout the entire chronological lifespan of yeast cultured under caloric restriction conditions. We show that Lithocholic Acid stimulates the aging-delaying cellular pattern and preserves such pattern because it specifically modulates the spatiotemporal dynamics of a complex cellular network. We demonstrate that this cellular network integrates certain pathways of lipid and carbohydrate metabolism, some intercompartmental communications, mitochondrial morphology and functionality, and liponecrotic and apoptotic modes of aging-associated cell death. Our findings indicate that Lithocholic Acid prolongs longevity of chronologically aging yeast because it decreases the risk of aging-associated cell death, thus increasing the chance of elderly cells to survive.