Design, Synthesis, Biological Evaluation, and Docking Study of Acetylcholinesterase Inhibitors: New Acridone‐1,2,4‐oxadiazole‐1,2,3‐triazole Hybrids

Abstract

In this study, novel acridone-1,2,4-oxadiazole-1,2,3-triazole hybrids were designed, synthesized, and evaluated for their acetylcholinesterase and butyrylcholinesterase inhibitory activity. Among various synthesized compounds, 10-((1-((3-(4-methoxyphenyl)-1,2,4-oxadiazol-5-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl)acridin-9(10H)-one 10b showed the most potent anti-acetylcholinesterase activity (IC50 = 11.55 μm) being as potent as rivastigmine. Also docking outcomes were in good agreement with in vitro results confirming the dual binding inhibitory activity of compound 10b.

Quinolone–Triazole Hybrids and their Biological Activities

“…Alzheimer's disease (AD) is the most common neurodegenerative syndrome and has emerged as the main cause of dementia among elderly people affecting cognitive characteristics such as intelligence, memory, language, and speech are overshadowed . The rapid growth of AD combined with medical and social issues has created an urgent need to develop new agents.…”

“…Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), two cholinesterases (ChEs), are responsible for the regulation of cholinergic neurotransmission, the decline of which leads to AD . Tacrine, quinoline‐based compound, acts on the AChE, was approved for the treatment of AD, while 1,2,3‐triazole subunit also exhibited excellent potency in inhibition of AChE .…”

“…Based on the aforementioned research results, a series of quinolone‐based 1,2,3‐triazole hybrids 16 (Fig. ) were assessed for their in vitro anti‐AChE and anti‐BChE inhibitory activities by Akbarzadeh et al . In spite of almost all derivatives were inactive against BChE (IC 50 : >100 μM), the majority of them exhibited considerable activities against AChE with IC 50 in a range of 7.31 to 88.10 μM.…”

Novel cinnamic acid–tryptamine hybrids as potent butyrylcholinesterase inhibitors: Synthesis, biological evaluation, and docking study

“…In this context and as a continuation of our previous works on the synthesis of novel anti‐AD compounds, here we designed a new series of cinnamic acid–tryptamine hybrids 7a–l and evaluated their activity against AChE and BChE . Kinetic and docking studies of the synthesized compounds were also performed.…”

Phthalimide‐Derived N‐Benzylpyridinium Halides Targeting Cholinesterases: Synthesis and Bioactivity of New Potential Anti‐Alzheimer's Disease Agents

“…Furthermore, several AChE inhibitors were designed based on the phthalimide pharmacophore . Therefore, in continuation of our efforts on the synthesis of bioactive compounds , herein we report synthesis, in vitro biological evaluation, and docking study of N ‐benzylpyridinium‐type compounds 7 bearing phthalimide scaffolds. The type and position of substituent on the N ‐benzyl residue were modified for structure–activity relationships (SAR) study.…”