Potential of Tryptamine Derivatives as Multi-Target Directed Ligands for Alzheimer's Disease: AChE, MAO-B, and COX-2 as Molecular Targets.

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, SR42, SR25, and SR10, displayed significant AChE inhibitory activity, with IC50 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 These values superseded the standard drug donepezil (1.96 µM).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, SR42 (IC50 = 43.21 µM) demonstrated superior inhibitory effects as compared to tryptamine and other derivatives. Moreover, SR22 (84.08%), SR24 (79.30%), and SR42 (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 SR42, 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.

Synthesis, biological screening and docking studies of some indole derivatives as potential antioxidant.

The present study envisioned some antioxidant candidates having 1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole (TRY), 3-(2-bromoethyl)indole (BEI) and 7-azindole (AI) nucleus. Derivatives of these indole molecules were synthesized and their scavenging activity for reactive oxygen species (ROS) investigated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. T3, T42 exhibited significant radical scavenging potential which is comparable to ascorbic acid (standard), while T36 appeared as most potent antioxidant by displaying better scavenging activity than standard molecule. Molecular docking study revealed good binding score and interactions of T36 with target human antioxidant enzyme (PDB code: 3MNG) validating the results of biological activity.

Computation-based experimentation: Identification of piperazine containing antidepressants.

Depression, a common mental disorder, is one of the major contributors to the overall global burden with more than 264 million individuals affected worldwide. Monoamine oxidase inhibitors (MAOIs) have well-known efficacy for treating depression and other related disorders. Herein we report the implementation of extensive in-silico calculations to predict the mono-amine inhibitory potential of an in-house library of piperazine-based compounds. In this connection, a multistep virtual screening protocol based on pharmacophore modeling, molecular docking and Quantitative Structure-Activity Relationship (QSAR) was carried out by MOE. Further, to assess its ability to cross the blood brain barrier, ADME properties of the compounds were predicted. Compounds predicted the highest enzyme inhibition by QSAR was synthesized for experimental validation. Both the synthesized compounds (I15 and I21) presented good strength against Monoamine Oxidase in in vitro enzyme inhibitory activity.