Phenolic and terpene compounds from Plectranthus amboinicus (Lour.) Spreng. Act as promising hepatic anticancer agents screened through in silico and in vitro approaches

Abstract

The present study aims to validate the anticancer potential of the phytocompounds namely carvacrol, thymol, alpha pinene, limonene, vanillin, cineole and syringic acid against apoptotic regulator target proteins through in silico approach. The drug likeness nature of the selected phytocompounds analyzed using SWISS ADME online server. The phytocompounds met the requirements of Lipinski, Ghose, Veber, Egan, and Muegge rules of violations and expected to be orally available. The phytocompounds pervading zero violations were further subjected to predict the various pharmacokinetic properties such as Adsorption, Distribution, Metabolism, Excretion and Toxicity (ADMET). The phytocompounds possess good ADMET properties and can be considered safe and further developed into active commercial anticancer drugs. Molecular docking analysis revealed that the phytocompounds displayed strong interactions with the apoptotic regulator target proteins (PDB IDs 3MK8, 3PK1, 4IDT, 4ZBF, 5FMI, 5LAY and 5MW7) and illustrated good binding affinity in the range of -4.8 to -6.7Kcal/mol. The phytocompound carvacrol shows good binding affinity with all target proteins (-5.3 to -6.7 Kcal/mol) thereby possessing appreciable bonded and non-bonded interactions with the binding pockets of target proteins. Thymol and syringic acid possess good interaction with the cancer target proteins next to carvacrol. Density Functional Theory (DFT) analysis demonstrated the high softness, low hardness and less energy gap between the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) and revealed the molecular stability and reactivity of the phytocompounds. Drug ability likeliness property studied against GPCR ligands, ion channel modulators, kinase inhibitors, nuclear receptor ligands, protease inhibitors and enzyme inhibitors predicted the moderate biological activity of the phytocompounds. MTT assay confirmed 50% reduction of HEK 293 cells in a dose-dependent mode and the CC50 value was recorded as 27.56μg/ml and 15.32μg/ml for the methanolic extract and the drug avastin respectively. Thus the findings of the in silico based studies demonstrated the promising apoptosis - modulating effect of the phytocompounds and fetch novel improvements for alternative medicine in the prevention and treatment of hepatic cancer.