Action Mechanism of Bioactive Compounds from Plants and Spices Mixture as Promising Anticancer Agents: In Silico Drug Design Predictions Targeting Cancer Cell Proliferation Through Cell Cycle Arrest Pathway

Although cancer has been the main reason for death for decades, until now, no safe certified drugs have been discovered to efficiently inhibit its progression. Currently, we aim to employ an in-silico model to predict the action mechanism of phenolic components that we previously demonstrated as inhibitors of colon, prostate and lung cancer. The work was performed by testing pharmacokinetics and pharmacodynamics proprieties of selected molecules. Four compounds: Kaempferol, chrysin, vanillin and p-hydroxybenzoic acid widely obeyed the five rules and the ADME/T criteria with minimum toxicity. Docking prediction recorded an intense affinity between kaempferol-CDK1(-17.72 +/- 0.02 kcal/mol), chrysin-CDK1 (-17.61 +/- 0.01 kcal/mol) and kaempferol-caspase 8 (-9.30 +/- 0.00 kcal/mol), chrysin-caspase 8 (-8.18 +/- 0.12 kcal/mol), vanillin-MMP9 (-9.83 +/- 0.04 kcal/mol) and p-hydroxybenzoic acid-Ca2 (-8.91 +/- 0.01 kcal/mol). Likewise, MMGBSA results demonstrated that these compounds are evidently bound to the targets' active sites with solid interactions. The passed compounds might target the responsible factors for transcription as inactivators. The molecular mechanism based on kaempferol and vanillin actions was predicted to target CDK1 and MMP9 via cell cycle arrest and apoptosis. All results were confirmed through RMSD analysis suggesting that kaempferol and vanillin are the best ligands to suppress cancer cell proliferation. Thus, these findings allowed us to imagine a potential molecular mechanism of these binaries, phenolic compounds/target proteins to lead further trails on cancer, of which the synergistic activity between phenolic compounds could promote the therapeutic capacity.