- Synthesis and anti-endoplasmic reticulum stress activity of N-substituted-2-arylcarbonylhydrazinecarbothioamides
-
Misfolded or unfolded proteins are accumulated in lumen of endoplasmic reticulum (ER) in ER stress condition. It has been implicated in many pathological conditions such as Alzheimer’s disease, diabetic retinopathy, atherosclerosis, β-cell apoptosis and lung inflammation. We found a series of N-substituted-2-arylcarbonylhydrazinecarbothioamides to potently decrease ER stress signal, showing up to almost 300-fold better activity than 1-hydroxynaphthoic acid and tauro-ursodesoxycholic acid, positive controls, respectively. Structure?activity relationship (SAR) study showed that 2-arylcarbonyl moiety is critical for the activity of the hydrazinecarbothioamide analogues and side chains tethering on thioamide moiety were relatively insensitive to the activity. Some analogues were found to consistently exert the potency under more physiologically relevant condition where ER stress was induced by palmitic acid. ER stress markers such as CHOP and phosphorylated eIF2α and PERK were accordingly decreased in western blotting upon treatment of compound 4h. Potential ER stress inhibitory activity and novel structures could provide a novel platform for new chemical chaperone and therapy for protein misfolding diseases.
- Choi, Hoon,Yun, Wheesahng,Lee, Jung-hun,Jang, Seoul,Park, Sang Won,Kim, Dong Hwan,Seon, Kyoung Pyo,Hyun, Jung-mi,Jeong, Kwiwan,Ku, Jin-mo,Nam, Tae-gyu
-
p. 2142 - 2152
(2019/11/03)
-
- Design, Synthesis and Antibacterial Evaluation of 1-[(1R,2S)-2-Fluorocyclopropyl]ciprofloxacin-1,2,4-triazole-5(4H)-thione Hybrids
-
A new class of 1-[(1R,2S)-2-fluorocyclopropyl]ciprofloxacin (CPFX)-1,2,4-triazole-5(4H)-thione hybrids 6a?–?6o was designed, synthesized and evaluated for their in?vitro antibacterial activities against a panel of clinically important drug-sensitive and d
- Gao, Yang,Na, Lu-Xin,Xu, Zhi,Zhang, Shu,Wang, A-Peng,Kai,Guo, Hui-Yuan,Liu, Ming-Liang
-
-
- Small molecule inhibitors of HIV RT Ribonuclease H
-
Two classes of compounds, thiocarbamates 1 and triazoles 2, have been identified as HIV RT RNase H inhibitors using a novel FRET-based HTS assay. The potent analogs in each series exhibited selectivity and were active in cell-based assays. In addition, sa
- Grandi, Martin Di,Olson, Matthew,Prashad, Amar S.,Bebernitz, Geraldine,Luckay, Amara,Mullen, Stanley,Hu, Yongbo,Krishnamurthy, Girija,Pitts, Keith,O'Connell, John
-
scheme or table
p. 398 - 402
(2010/04/05)
-
- Microwave-assisted rapid synthesis of thiosemicarbazide derivatives
-
Rapid and highly efficient synthesis of thiosemicarbazides by the coupling of isothiocyanate and carboxylic acid hydrazides in small amount of a polar solvent is achieved under microwave irradiation by using a domestic microwave oven. The reaction proceed
- Zamani, Khosrow,Faghihi, Khalil,Bagheri, Shirindokht,Kalhor, Mahdi
-
p. 2716 - 2718
(2007/10/03)
-
- Synthesis and structure determination of some oxadiazole-2-thione and triazole-3-thione galactosides
-
The syntheses of 5-pyridyl-3(β-D-galactopyranosyl)-1,3,4-oxadiazole-2-thiones 3a-3c and 5-pyridyl-2(β-D-galactopyranosyl)-4-benzyl-l,2, 4-triazole-3-thiones 6a-6c are reported. The existence of N-galactosides - not S-galactosides - was proven by IR and 15N NMR spectroscopy. The structures of the final products and the intermediates were elucidated by IR, 1H, 13C and 15N NMR spectroscopy and mass spectrometry.
- Ahmad, Roshan,Iqbal, Rashid,Akhtar, Humaira,Duddeck, Helmut,Stefaniak, Lech,Sitkowski, Jerzy
-
p. 1671 - 1682
(2007/10/03)
-
- Synthesis and antimicrobial activity of 2,4-dihydro-4-benzyl-5-(isomeric pyridyl)-3H-1,2,4-triazole-3-thiones
-
intramolecular cyclization of the three isomeric 1,4-disubstituted thiosemicarbazides 3a-c in aqueous sodium hydroxide affords 2,4-dihydro-4-(benzyl)-5-(isomeric pyridyl)-3H-1,2,4-triazole-3-thiones 4a-c.The antibacterial activity of these compounds has been determined against seventeen, gram positive and gram negative microorganisms.
- Iqbal, Rashid,Rama, Nasim H.,Ahmad, Nasir,Zamani, Khosrow,Ebrahim, Samia,Iqbal, Nasir
-
p. 506 - 509
(2007/10/03)
-