| Summary: | Extensive research has been dedicated to develop compounds that can target multiple aspects of Alzheimer’s disease (AD) treatment due to a growing understanding of AD’s complex multifaceted nature and various interconnected pathological pathways. In the present study, a series of biological assays were performed to evaluate the potential of the tryptamine analogues synthesized earlier in our lab as multi-target-directed ligands (MTDLs) for AD. To assess the inhibitory effects of the compounds, various in vitro assays were employed. Three compounds, <b>SR42</b>, <b>SR25</b>, and <b>SR10,</b> displayed significant AChE inhibitory activity, with IC<sub>50</sub> values of 0.70 µM, 0.17 µM, and 1.00 µM, respectively. These values superseded the standard drug donepezil (1.96 µM). In the MAO-B inhibition assay, <b>SR42</b> (IC<sub>50</sub> = 43.21 µM) demonstrated superior inhibitory effects as compared to tryptamine and other derivatives. Moreover, <b>SR22</b> (84.08%), <b>SR24</b> (79.30%), and <b>SR42</b> (75.16%) exhibited notable percent inhibition against the COX-2 enzyme at a tested concentration of 100 µM. To gain insights into their binding mode and to validate the biological results, molecular docking studies were conducted. Overall, the results suggest that <b>SR42</b>, a 4,5 nitro-benzoyl derivative of tryptamine, exhibited significant potential as a MTDL and warrants further investigation for the development of anti-Alzheimer agents.
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