Design, Synthesis, and Evaluation of Novel 2H-Benzo[b][1,4]thiazin-3(4H)-one Derivatives as New Acetylcholinesterase Inhibitors

Abstract

Alzheimer’s disease (AD) is a slowly progressive neurodegenerative disease that causes dementia in people aged 65 and over. In the present study, a series of thiadiazole hybrid compounds with benzothiazine derivatives as acetylcholinesterase inhibitors were developed and evaluated for their biological activity. The AChE and BChE inhibition potentials of all compounds were evaluated by using the in vitro Ellman method. The biological evaluation showed that compounds 3i and 3j displayed significant inhibitory activity against AChE. Compounds 3i and 3j showed IC50 values of 0.027 µM and 0.025 µM against AChE, respectively. The reference drug donepezil (IC50 = 0.021 µM) also showed significant inhibition against AChE. Further docking simulation also revealed that these compounds (3i and 3j) interacted with the active site of the enzyme similarly to donepezil. The antioxidant study revealed that compounds 3i and 3j exhibited greater antioxidant effects. An in vitro blood–brain barrier permeability study showed that compounds 3i and 3j are promising compounds against AD. The cytotoxicity study of compounds 3i and 3j showed non-cytotoxic with an IC50 value of 98.29 ± 3.98 µM and 159.68 ± 5.53 µM against NIH/3T3 cells, respectively.

Synthesis and Anticancer Activities of Pyrazole–Thiadiazole-Based EGFR Inhibitors

“…After the reaction was complete, the mixture was cooled, and the precipitated product was filtered and purified by recrystallization with ethanol. 32 2-((5-(Ethylamino)-1,3,4-thiadiazol-2-yl)thio)-1-(5-(4-nitrophenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)ethan-1-one (6a): yield: 81%, mp: 161.7−162.3 °C. 1 H-NMR (300 MHz, DMSO-d 6 ): δ = 1.17 (3H, t, J = 7.…”

“…0.001 mol of K 2 CO 3 was then added, and the mixture was refluxed overnight. After the reaction was complete, the mixture was cooled, and the precipitated product was filtered and purified by recrystallization with ethanol …”

“…After the reaction was complete, the mixture was cooled, and the precipitated product was filtered and purified by recrystallization with ethanol. 32 …”

Design, Synthesis, and In Vitro and In Silico Approaches of Novel Indanone Derivatives as Multifunctional Anti-Alzheimer Agents

“…Only 200 μL of methanol was used for the blank reading, while the control reading required the usage of 100 μL each of methanol and the DPPH solution. Following incubation, a spectrophotometric measurement at 517 nm was carried out. , …”

Major Bioactive Prenylated Flavonoids from Humulus lupulus L., Their Applications in Human Diseases and Structure-Activity Relationships (SAR) – A Review

“…with donepezil have been reported in various recently reported studies. [138][139][140][141][142][143][144][145][146][147][148][149][150][151][152][153][154][155] The interactions between the target protein and drug was reported as H bonds with Tyr122, Phe293, Arg294, alkyl bonds with Leu287, Trp284, and pipi stacking with Trp84, and carbon-hydrogen bond with Ser291, Val292, Tyr335. 156 The main interactions for donepezil were reported for H bonds, hydrophobic and pi-interactions with Trp88, Trp279, Phe288, Phe290, Phe330, Tyr334, Arg289.…”