Anticancer potential of secondary metabolites of Piper nigrum against MOA B, AIF, CYP and EGFR proteins: In silico study

Context: Searching for novel anticancer-leading drugs is a current major concern for providing better treatment outcomes. Piper nigrum is one of the spice plants used as an anticancer in traditional medicine. Many studies reported the secondary metabolite content of P. nigrum. Some have been evaluated as anticancer agents, but many still need to be studied. Aims: To evaluate the in silico anticancer activity of P. nigrum secondary metabolites. Methods: Cheminformatics and bioinformatics analysis were used to investigate drug-likeness, toxicity, pharmacokinetics, and drug interaction against enzymes involved in reactive oxygen species production and cell growth. Results: Ten out of twenty-five compounds qualify as drugs according to the rules of Lipinski, Veber, Egan, Ghose, and Muegge, and they met the pharmacokinetic parameters. A molecular docking study showed that seven compounds showed a good affinity for enzymes involved in triggering cellular oxidative stress and cell death. Furthermore, piperine, piperidine derivatives, and piperettin may inhibit the cancer cell's growth due to their affinity with epidermal growth factor receptor (EGFR) compared to erlotinib. Of all these compounds, (2E,4E,8E)-9-(benzo[d][1,3]dioxol-5-yl)-1-(piperidine-1-yl)nona-2,4,8-trien- 1-one showed the best affinity with EGFR, monoamine oxidase B, apoptosis-inducing factor, and cytochrome P450. Conclusions: Besides piperine and piperidine derivatives, other compounds in P. nigrum, such as piperamide; piperamine; sarmentine; trichosta; piperettine; and pyrrolidine, 1-[5-(1,3-benzodioxol-5-yl)- 1 - oxo -2,4-pentadienyl]-,(E,E)-, also have promising potential as an anticancer.