Synthesis of tacrine-lophine hybrids via one-pot four component reaction and biological evaluation as acetyl- and butyrylcholinesterase inhibitors

Abstract

a b s t r a c tA novel series of tacrine-lophine hybrids was synthesized and tested for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) with IC 50 in the nanomolar concentration scale. The key step is the one-pot four component condensation reaction of 9-aminoalkylamino-1,2,3,4-tetrahydroacridines, benzil, different substituted aromatic aldehydes and NH 4 OAc, using InCl 3 as the best catalyst. Tacrine-lophine hybrids were found to be potent and selective inhibitors of cholinesterases. As an extension of the four component approach to tetrasubstituted imidazoles, a new series of bis-(2,4,5-triphenyl-1H-imidazoles) or bis(n)-lophines was tested against AChE and BuChE.

Current advances in the synthesis and biological potencies of tri- and tetra-substituted 1H-imidazoles

“…Several tetra-substituted imidazoles, a novel series of bis-(2,4,5-triphenyl-1H -imidazoles), bis(n)-lophines were synthesized via the four-component strategy and tested against AChE and BuChE, and several of them were found to be active and selective inhibitors of these 2 targets. The non-tacrine bis(8)-lophine 262c showed selective AChE inhibitory potency [213].…”

“…The capability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) with IC 50 values in a nanomolar concentration scale were evaluated for these dimers [213]. A new series of hybrids tacrine-2,4,5-triphenyl-1H -imidazole (or tacrine-lophine hybrids) were synthesized as inhibitors of AChE and BuChE.…”

Multifunctional properties of novel tacrine congeners: cholinesterase inhibition and cytotoxic activity

“…The multifunctional properties of tacrine derivatives, which have been discovered in recent years continue to stimulate significant interest in this field of chemistry (Anand & Singh, 2013;Čolović, Krstić, Lazarević-Pašti, Bondžić, & Vasić, 2013;Hamulakova et al, 2016;Hamulakova, Janovec, Soukup, Jun, & Kuca, 2017;Kozurkova & Kristian, 2014;Martorana et al, 2016;Melo et al, 2012;Milelli, Simone, & Ticchi, 2017;Panek, Wichur, Godyń, Pasieka, & Malawska, 2017;Proctor & Harvey, 2000;Thiratmatrakul et al, 2014;Tumiatti et al, 2010;Viayna, Sabate, & Muñoz-Torrero, 2013;Wu et al, 2017). In addition to their two basic trades concerning the inhibition of AChE/butyryl cholinesterase (AChE/BChE) and Aβ aggregation, tacrine congeners are also characterized by a variety of other features such as the ability to protect against oxidative stress, β-secretase and M 1 muscarinic receptors (Da Costa et al, 2013;Ježek, Hlaváček, & Šebestík, 2017;Kožurková et al, 2011;Lopes et al, 2017;McHardy, Wang, McCowen, & Valdez, 2017;Soukup et al, 2013;Szymański et al, 2013). Extensive overviews concerning the mode of action of these esterase systems have been the topic of several articles (Boulebd et al, 2017;Guzior, Wieckowska, Panek, & Malawska, 2015;Parveen & Kumar, 2005).…”

A Platform for Screening Potential Anticholinesterase Fractions and Components Obtained fromAnemarrhena asphodeloidesBge for Treating Alzheimer’s Disease

“…Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the central nervous system (CNS), characterized by deposits of aberrant proteins, namely, β -amyloid (A β ) and τ -protein, loss of synapses, death of cholinergic neurons, and oxidative stress [1, 2]. The etiopathogenesis of AD still remains unknown, although the neurodegeneration leads to remarkable reduction of neurotransmitter acetylcholine at the synaptic clefts [3, 4].…”