92539-18-9Relevant articles and documents
Design and development of novel thiazole-sulfonamide derivatives as a protective agent against diabetic cataract in Wistar rats via inhibition of aldose reductase
Yin, Liang,Zhang, Mingxue,He, Tiangeng
, p. 63 - 70 (2021/10/01)
In recent years, ALR2 (aldose reductase) inhibitors have attracted attention for their effective ability to reduce the progression of diabetes-associated cataracts. Therefore, in the present article, we intended to develop novel thiazole-sulfonamide hybrids as a potent inhibitor of ALR2. These molecules significantly inhibited the ALR2 level in the rat lenses homogenate, where the most potent compound 7b showed activity comparable to sorbinil as standard. In Wistar rats, compound 7b improved the insulin level and body weight of the experimental animal together with a reduction in the glucose output. Compound 7b showed a significant reduction in the expression of ALR2 in rat lenses in western blot analysis.
Substituted 2-thioxothiazolidin-4-one derivatives showed protective effects against diabetic cataract via inhibition of aldose reductase
Huang, Wanrong,Zhang, Yue,Liang, Xu,Yang, Lichun
, (2020/04/07)
In an effort to develop a new class of potent aldose reductase inhibitors against diabetic cataracts, a series of novel 2-thioxothiazolidine-4-one derivatives was synthesized in excellent yields via a facile synthetic route. These compounds were tested against aldehyde (ALR1) and aldose reductase (ALR2) enzymes, where they showed considerable inhibitory activity. Among the tested derivatives, compound 6e showed selective and excellent inhibition of ALR2 over ALR1. The experimental diabetes was induced by the intraperitoneal administration of streptozotocin in male Wistar rats. Compound 6e showed positive modulation of body weight, blood glucose, and blood insulin levels in diabetic rats. Compound 6e also showed ALR2 inhibition as evidenced by Western blot analysis in lens homogenates of Wistar rats having cataract. The docking study of 6e was also performed inside the active site of ALR2 to enumerate the key contacts for inhibitory activity.
INHIBITORS OF MUTANT ISOCITRATE DEHYDROGENASES AND COMPOSITIONS AND METHODS THEREOF
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, (2018/07/29)
The invention provides novel chemical compounds useful for treating cancer, or a related disease or disorder thereof, and pharmaceutical composition and methods of preparation and use thereof.
Rational Design and Multibiological Profiling of Novel Donepezil-Trolox Hybrids against Alzheimer's Disease, with Cholinergic, Antioxidant, Neuroprotective, and Cognition Enhancing Properties
Cai, Pei,Fang, Si-Qiang,Yang, Xue-Lian,Wu, Jia-Jia,Liu, Qiao-Hong,Hong, Hao,Wang, Xiao-Bing,Kong, Ling-Yi
, p. 2496 - 2511 (2017/11/21)
A novel series of donepezil-trolox hybrids were designed, synthesized, and evaluated as multifunctional ligands against Alzheimer's disease (AD). Biological assays showed that these derivatives possessed moderate to good inhibitory activities against acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B) as well as remarkable antioxidant effects. The optimal compound 6d exhibited balanced functions with good inhibition against hAChE (IC50 = 0.54 μM) and hMAO-B (IC50 = 4.3 μM), significant antioxidant activity (41.33 μM IC50 by DPPH method, 1.72 and 1.79 trolox equivalent by ABTS and ORAC methods), excellent copper chelation, and Aβ1-42 aggregation inhibition effect. Furthermore, cellular tests indicated that 6d has very low toxicity and is capable of combating oxidative toxin (H2O2, rotenone, and oligomycin-A) induced neurotoxicity. Most importantly, oral administration of 6d demonstrated notable improvements on cognition and spatial memory against scopolamine-induced acute memory deficit as well as d-galactose (d-gal) and AlCl3 induced chronic oxidative stress in a mouse model without acute toxicity and hepatotoxicity. In summary, both in vitro and in vivo results suggested that 6d is a valuable candidate for the development of a safe and effective anti-Alzheimer's drug.
Design and development of a novel chalcone derivative as an anticholinesterase inhibitor for possible treatment of dementia
Zhao, Fu-Chun,Wu, Yan,Song, Xiao-Jie
, p. 3311 - 3317 (2017/07/17)
Background: Cognitive decline (e.g., memory loss), which mainly occurs in the elderly, is termed dementia. In the present study, we intended to explore the cholinesterase inhibitory activity of some novel synthesized chalcones, together with their effect on β-amyloid anti-aggregation. Material/Methods: A novel class of chalcone derivatives have been synthesized and characterized by FT-IR,1H-NMR,13C-NMR, and mass and elemental analysis. These derivatives were later used for the determination of acetylcholinesterase (AChE) inhibitory and β-amyloid anti-aggregation activity. Results: The results of the study showed that among the developed compounds, 8g inhibits AChE more prominently than BuChE, as suggested by a selectivity index (SI) of 2.88. Furthermore, the most potent compound, 8g, showed considerable action in inhibition of β-secretase and Aβ aggregation, but not as prominent as that of curcumin as a standard. Conclusions: In conclusion, our study revealed a novel class of chalcone derivatives as a selective inhibitor of AChE with considerably action against β-secretase and Aβ aggregation. Our results may be useful in developing AD drug therapy and warrant further investigation to generate more advanced analogues.
Design, synthesis, and biological evaluation of novel 4-aminopiperidinyl-linked 3,5-disubstituted-1,2,6-thiadiazine-1,1-dione derivatives as HIV-1 NNRTIs
Liu, Tao,Huang, Boshi,Tian, Ye,Liang, Xin,Liu, Hong,Liu, Huiqing,Zhan, Peng,De Clercq, Erik,Pannecouque, Christophe,Liu, Xinyong
, p. 887 - 893 (2015/06/23)
Based on the hybridization of the privileged fragments in DABO and DAPY-typed HIV-1 NNRTIs, a novel series of 4-aminopiperidinyl-linked 3,5-disubstituted-1,2,6-thiadiazine-1,1-dione derivatives were designed, synthesized, and evaluated for their in vitro
