| Autor: |
Sagar SR; Department of Medicinal Chemistry , B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre , S. G. Highway , Thaltej, Ahmedabad , 380054 Gujarat , India.; Institute of Pharmacy , NIRMA University , S. G. Highway , Chandlodia, Gota, Ahmedabad , 382481 Gujarat , India., Singh DP; Department of Pharmacology and Toxicology , B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre , S. G. Highway , Thaltej, Ahmedabad , 380054 Gujarat , India., Panchal NB; Department of Medicinal Chemistry , B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre , S. G. Highway , Thaltej, Ahmedabad , 380054 Gujarat , India.; Institute of Pharmacy , NIRMA University , S. G. Highway , Chandlodia, Gota, Ahmedabad , 382481 Gujarat , India., Das RD; Department of Medicinal Chemistry , B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre , S. G. Highway , Thaltej, Ahmedabad , 380054 Gujarat , India., Pandya DH; Department of Medicinal Chemistry , B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre , S. G. Highway , Thaltej, Ahmedabad , 380054 Gujarat , India., Sudarsanam V; Department of Medicinal Chemistry , B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre , S. G. Highway , Thaltej, Ahmedabad , 380054 Gujarat , India., Nivsarkar M; Department of Pharmacology and Toxicology , B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre , S. G. Highway , Thaltej, Ahmedabad , 380054 Gujarat , India., Vasu KK; Department of Medicinal Chemistry , B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre , S. G. Highway , Thaltej, Ahmedabad , 380054 Gujarat , India. |
| Abstrakt: |
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. |
