ACS Chemical Neuroscience p. 1663 - 1679 (2018)
Update date:2022-08-15
Topics:
Sagar, Sneha R.
Singh, Devendra Pratap
Panchal, Nirupa B.
Das, Rajesh D.
Pandya, Dhaivat H.
Sudarsanam, Vasudevan
Nivsarkar, Manish
Vasu, Kamala K.
Alzheimer's disease (AD) is associated with multiple neuropathological events including β-site amyloid precursor protein cleaving enzyme-1 (BACE-1) inhibition and neuronal inflammation, ensuing degeneracy, and death to neuronal cells. Targeting such a complex disease via a single target directed treatment was found to be inefficacious. Hence, with an intention to incorporate multiple therapeutic effects within a single molecule, multitarget-directed ligands (MTDLs) have been evolved. Herein, for the first time, we report the discovery of novel thiazolyl-thiadiazines that can serve as MTDLs as evident from the in vitro and in vivo studies. These MTDLs exhibited BACE-1 inhibition down to micromolar range, and results from the in vivo studies demonstrated efficient anti-inflammatory activity with inherent gastrointestinal safety. Moreover, compound 6d unveiled noteworthy antioxidant, antiamyloid, neuroprotective, and antiamnesic properties. Overall, results of the present study manifest the potential outcome of thiazolyl-thiadiazines for AD treatment.
View MoreContact:+86 021-51698675
Address:1701, Jielong Plaza, No.618 Pingliang Rd, ShangHai,China
Contact:+86-21-38682181
Address:shanghai ,china
Changyi Xinxing Technology Development Co., Ltd.
Contact:0086-510-86651065(Time Zone:8),86651656
Address:94 Yingbinxilu WestRoad, Huangtu Town, Jiangyin City, Jiangsu, China
Contact:86-574-83851061 86-574-87083208
Address:Room 905, No.3 Building,East Business Center, 456 Xingning Road, Ningbo City,China
Contact:
Address:
Doi:10.1016/S0022-328X(00)84568-4
(1971)Doi:10.1074/jbc.RA118.001980
(2018)Doi:10.1039/c9cy01791g
(2019)Doi:10.1039/c5ra05418d
(2015)Doi:10.1002/hc.20665
(2011)Doi:10.1021/j150662a021
(1984)