- Lysosomal Reacidification Ameliorates Vinyl Carbamate-Induced Toxicity and Disruption on Lysosomal pH
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Ethyl carbamate (EC) is a carcinogen toxicant, commonly found in fermented foods and beverages. The carcinogenic and toxic possibility of EC is thought to be related to its metabolite vinyl carbamate (VC). However, we found interesting mechanisms underlying VC-induced toxicity in this study, which were greatly different from EC. We first conducted a simple synthesis procedure for VC and found that VC possessed higher toxicity but failed to regulate levels of reactive oxygen species, glutathione, and autophagy. Notably, VC treatment resulted in upregulation of lysosomal pH, which was responsible for its cytotoxicity. Cyclic adenosine monophosphate (cAMP) pretreatment could enhance restoration of lysosomal acidity and ameliorate VC-induced damage. Inhibition of protein kinase A and cystic fibrosis transmembrane conductance regulator can block cAMP-induced cytoprotection. Together, our results provided the evidence for novel mechanisms of toxicity and possible protection method under VC exposure, which might give new perspectives on the study of EC-induced toxicity.
- Chen, Wei,Cui, Sunliang,Hu, Dongwen,Li, Yuting,Qi, Jifeng
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p. 8951 - 8961
(2020/09/16)
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- Hepatitis C inhibitor tri-peptides
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Disclosed herein are compounds of formula (1): wherein R1is hydroxy or NHSO2R1Awherein R1Ais (C1-8)alkyl, (C3-7)cycloalkyl or {(C1-6)alkyl-(C3-7)cycloalkyl}, which are all optionally substituted from 1 to 3 times with halo, cyano, nitro, O—(C1-6)alkyl, amido, amino or phenyl, or R1Ais C6or C10aryl which is optionally substituted from 1 to 3 times with halo, cyano, nitro, (C1-6)alkyl, O—(C1-6) alkyl, amido, amino or phenyl; R2is (C4-6)cycloalkyl; R3is t-butyl or (C5-6) cycloalkyl and R4is (C4-6)cycloalkyl; or a pharmaceutically acceptable salt thereof. The compounds are useful as inhibitors of HCV NS3 protease.
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- Hepatitis C inhibitor tri-peptides
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Disclosed herein are compounds of formula (1): wherein Ris hydroxy or NHSO2Rwherein Ris (C1-8)alkyl, (C3-7)cycloalkyl or {(C1-6)alkyl-(C3-7)cycloalkyl}, which are all optionally substituted from 1 to 3 times with halo, cyano, nitro, O-(C1-6)alkyl, amido, amino or phenyl, or Ris C6 or C10 aryl which is optionally substituted from 1 to 3 times with halo, cyano, nitro, (C1-6)alkyl, O-(C1-6) alkyl, amido, amino or phenyl; Ris (C4-6)cycloalkyl; Ris t-btuyl or (C5-6) cycloalkyl and Ris (C4-6)cycloalkyl; or a pharmaceutically acceptable salt thereof. The compounds are useful as inhibitors of HCV NS3 protease.
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- New applications of the protecting group di-(4-methoxyphenyl)methyl: N-protection of urethanes and uridines, and efficient removal by either ceric ammonium nitrate/silica or 2,3-dichloro-5,6-dicyanoquinone
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The protecting group di-(4-methoxyphenyl)methyl, removable by ceric ammonium nitrate on silica or 2,3-dichloro-5,6-dicyanoquinone, is shown to facilitate syntheses of urethanes (eg vinyl urethane, 1a) and uridine derivatives (eg 2-O-allyluridine, 8).
- AbuSbeih, Khaled,Bleasdale, Christine,Golding, Bernard T,Kitson, Sean L
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p. 4807 - 4810
(2007/10/02)
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- Vinyl chloroformates and preparation
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Vinyl chloroformates are described of formula STR1 in which: R1 =R2 =Cl, Br or a saturated 1-4 carbon atom alkyl or together they form a cycloaliphatic ring of 4-8 carbon atoms; R3 =H when R1 or R2 =a
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