In silico prediction of some pharmacokinetic, safety, biological activity and molecular docking studies of 1-piperazine indole hybrid with nicotinic amide and nicotinic acid and their analogues.

Background: In silico predictions are now being utilized in drug discovery and design to assess the physicochemical, pharmacokinetics, and safety properties of compounds at the beginning of the drug discovery process. This early evaluation of the physicochemical, pharmacokinetics, and safety properties of compounds helps the researchers to invest their time and resources only in the best prospective lead compounds by eliminating compounds with a low chance of success.

Objective: The purpose of this study was to explore a promising lead compound designed from 1-piperazine indole hybrid with nicotinic amide and nicotinic acid analogs targeted on Trypanosoma brucei phosphofructokinase for Trypanosomiasis activity by using in silico predictions strategy.

Results: The physicochemical, safety, pharmacokinetic, and biological activity properties of those molecules were predicted by using ADMETlab 2.0, ACD labs Chem Sketch software version 14.0, Molinspiration software, and MolPredictX online tool. Our results indicate that several promising candidates exhibit favorable characteristics. Based on Molinspiration software both nicotinic acid and nicotinic amide derivatives showed higher kinase inhibitor activity and all nicotinic acid derivatives revealed enzyme inhibitors and GPCR ligand activity. According to the MolPredictX online tool, the most biologically active derivatives were NA-4, NA-11, and NAD-11.

Conclusion: Overall, our findings offer valuable insights into the potential efficacy and safety of these compounds. It appears that almost all of the compounds have successfully passed the pharmacokinetic evaluations and integration of nicotinic acid into indole appears to be more beneficial than nicotinic amide regarding certain biological activities.