Synthesis, anticholinesterase and antioxidant potentials of ketoesters derivatives of succinimides: a possible role in the management of Alzheimer’s

Abstract

BackgroundBased on the pharmacological potency and structural features of succinimides, this study was designed to synthesize new ketoesters derivatives of succinimides. Furthermore, the synthesized compounds were evaluated for their possible anticholinesterase and antioxidant potentials. The compounds were synthesized by organocatalytic Michael additions of α-ketoesters to N-aryl maleimides. Acetyl and butyrylcholinesterase inhibitory activities were determined using Ellman’s spectrophotometric assay. The antioxidant activity was performed with DPPH and ABTS free radicals scavenging assay.ResultsThe Michael additions of α-ketoesters to maleimides was promoted by 8-hydroxyquinoline. The organocatalyst (8-hydroxyquinoline, 20 mol %) produced the compounds in relatively shorter time (20–24 h) and with excellent isolated yields (84-98 %). The synthesized compounds (1–4) showed outstanding acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory potentials, i.e., 98.75 and 90.00 % respectively for compound 2, with IC50 < 0.1 μg/mL. Additionally, compounds 1–4 revealed moderate antioxidant activity at different concentrations. In DPPH free radical scavenging assay, compound 1 showed dominant result with 72.41 ± 0.45, 52.49 ± 0.78 and 35.60 ± 0.75 % inhibition at concentrations of 1000, 500 and 250 μg/mL respectively, IC50 value of 440 μg/mL. However, the free radical scavenging was better when used ABTS free radicals. In ABTS free radicals scavenging assay compound 1 exhibited 88.51 ± 0.62 % inhibition at highest tested concentration i.e., 1000 μg/mL.ConclusionsHerein, we have synthesized four ketoesters derivatives of succinimides in a single step reaction and high yields. As a highlight, we have showed a first report on the anticholinesterase and antioxidant potentials of succinimides. All the compounds showed overwhelming enzyme inhibitions and moderate antioxidant potentials.Graphical AbstractGraphical representation of synthesis, anticholinesterase and antioxidant potentials of ketoester derivatives of succinimides.Electronic supplementary materialThe online version of this article (doi:10.1186/s13065-015-0107-2) contains supplementary material, which is available to authorized users.

Antibacterial and antifungal potentials of the solvents extracts from Eryngium caeruleum, Notholirion thomsonianum and Allium consanguineum

“…The antimicrobial agents may interrupt the synthesis of metabolites which are necessary for the basic integrity of microbes including bacteria and fungi [55, 56]. However, the main problem with the use of antimicrobial and other drugs is the hazardous and toxic effects associated with their use [57, 58]. Secondly, many microbes develop resistance to a specific group of drugs and they become less susceptible to that specific drug [55].…”

Neurologically Potent Molecules from Crataegus oxyacantha; Isolation, Anticholinesterase Inhibition, and Molecular Docking

“…Major symptoms associated with AD are memory loss, behavioral turbulence and mood disturbance in routine life (Kumar et al, 1998). Several biochemical pathways are followed for the management of AD but one of the most established approach is the inhibition of acetylcholinesterase (AChE) (Zeb et al, 2014; Ahmad et al, 2015; Kamal et al, 2015; Sadiq et al, 2015). The AChE is found in excitable tissues in most erythrocytes and in the placental tissues while butyrylcholinesterase (BChE) is present in nervous system, liver and plasma (Massoulié et al, 1993).…”

“…Several cholinesterase inhibitors from natural and synthetic sources are available like galantamine, donepezil, rivastigmine, and tacrine (Schulz, 2003). Numerous researchers have also shown that oxidative stress is an early pathogenic event in AD (Sadiq et al, 2015). Therefore, they supplement their anticholinesterase with antioxidants as free radicals scavengers.…”

“…Therefore, they supplement their anticholinesterase with antioxidants as free radicals scavengers. A constant research is going in the field of AD, which brought several reports from natural product sources and synthetic origin (Ayaz et al, 2014; Sadiq et al, 2015). However, most of these remedies are associated with severe side effects, low efficacy or availability.…”

Molecular modeling studies for exploring structural requirement of acetylcholinesterase inhibitors

“…The ACh hydrolyzes to produce choline and acetyl group through the biocatalyst acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in the synaptic region [1]. Inhibition of AChE enzyme can sustain the ACh depletion, which is the main strategy for the treatment of AD.…”