Design and Synthesis of New Dual Binding Site Cholinesterase Inhibitors: in vitro Inhibition Studies with in silico Docking

Abstract

Cholinesterases (ChEs) play a vital role in the regulation of cholinergic transmission. The inhibition of ChEs is considered to be involved in increasing acetylcholine level in the brain and thus has been implicated in the treatment of Alzheimer’s disease. We have designed and synthesized a series of novel indole derivatives and screened them for inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Most of the tested compounds exhibited inhibitory activity against AChE and BChE. Among them 4f and 6e showed the highest AChE inhibitory activity with IC50 91.21±0.06 and 68.52±0.04 μM, respectively. However compound 5a exhibited the highest inhibitory activity against BChE (IC50 55.21±0.12 μM).

Synthesis, characterization, lipoxygenase inhibitory activity and in silico molecular docking of biaryl bis(benzenesulfonamide) and indol-3-yl-hydrazide derivatives

“…The structures of these compounds were established with the aid of spectroscopic data and in complete agreement with the reported molecules [40,41].…”

“…In an ongoing effort in search of potent LOX inhibitors, we have already reported the LOX inhibition activity of some indole-based Schiff bases [40]. In this paper, we report the facile synthesis of new biphenyl bis(benzenesulfonamides) 2a-3f along with the known indol-3-yl-derivatives 4-6 [41], LOX inhibition and structure-activity relationship (SAR) of compounds 2a-6. Docking studies of the most active compounds 2a and 4e were performed.…”

Pyridine sulfonamide as a small key organic molecule for the potential treatment of type-II diabetes mellitus and Alzheimer’s disease: In vitro studies against yeast α-glucosidase, acetylcholinesterase and butyrylcholinesterase

“…The high desire and need for the development of potent dual inhibitors for the treatment of both AD and DM [12,27], and our continued research efforts for the synthesis and evaluation of AChE, BChE and α-glucosidase inhibitors [22][23][24][25][26]. In this paper, we report the synthesis of a series of new pyridine sulfonamide derivatives and their in vitro AChE, BChE and α-glucosidase inhibition activities and in silico molecular modeling studies to uncover the binding patterns of these compounds with respective targeted proteins.…”

Synthesis and DPPH scavenging assay of reserpine analogues, computational studies and in silico docking studies in AChE and BChE responsible for Alzheimer's disease

“…Indole alkaloids are well known due to their extensive biological importance (Inman, Moody, 2013;Yar et al, 2014b) including AChE (Monte-Millán et al, 2006;Ismail et al, 2012;Munoz-Ruiz et al, 2005) and BChE (Boga et al, 2011;Jakubowska et al, 2012;Yar et al, 2014a) inhibition activities. Compounds containing indole skeleton were also found to be the dual binding site AChE inhibitors, which in turn has a potential in disease modifying agents (Munoz-Ruiz et al, 2005) (Figure 2, a and b).…”

“…Compounds containing indole skeleton were also found to be the dual binding site AChE inhibitors, which in turn has a potential in disease modifying agents (Munoz-Ruiz et al, 2005) (Figure 2, a and b). Thus, there is a great deal of interest to develop dual binding site AChE inhibitors as a means to control AD (Monte-Millán et al, 2006;Yar et al, 2014a). Tacrine-melatonin hybrids (Figure 2, c), which were potent inhibitors of human AChE and showed high oxygen radical absorbance capacity, were also synthesized (Franco, Isabel, 2006).…”