Gupta_2022_Pharmaceutics_15_

As acetylcholinesterase (AChE) plays a crucial role in advancing Alzheimer's disease (AD), its inhibition is a promising approach for treating AD. Sulindac is an NSAID of the aryl alkanoic acid class, consisting of a indene moiety, which showed neuroprotective behavior in recent studies. In this study, newer Indene analogs were synthesized and evaluated for their in vitro AChE inhibition. Additionally, compared with donepezil as the standard drug, these Indene analogs were accessed for their cell line-based toxicity study on SH-SY5Y cell line. The molecule SD-30, having hydrogen bond donor (HBD) at para-position, showed maximum AChE inhibition potential (IC(50) 13.86 +/- 0.163 microM) in the indene series. Further, the SD-30 showed maximum BuChE inhibition potential (IC(50) = 48.55 +/- 0.136 microM) with a selectivity ratio of 3.50 and reasonable antioxidant properties compared to ascorbic acid (using DPPH assay). SD-30 (at a dose level: of 10 microM, 20 microM) effectively inhibited AChE-induced Abeta aggregation and showed no significant toxicity up to 30 mM against SH-SY5Y cell lines.