Quantum chemical, ADMET and molecular docking studies of ferulic acid amide derivatives with a novel anticancer drug target

Cancer is among the major health problems and leading cause of deaths worldwide. As per the World Health Organization report, the number of cancer patients will increase up to ae30% by the year of 2030. So there is a necessity to invent new and effective anticancer agents. Peptide deformylase, a member of hydrolases family which removes the formyl group from initiating methionine of nascent peptides, recently proved as novel target for anticancer drugs. Here, theoretical studies of ferulic acid amide derivatives have been performed for geometry optimization, calculation of electronic properties and structural parameters by using density functional theory employing B3LYP correlation at 6-311 G** basis set by Gaussian 09 suite. Calculations of highest occupied molecular orbital and lowest unoccupied molecular orbital energies showed the eventual charge transfer interaction within the molecules. The absorption, distribution, metabolism, excretion and toxicity parameters were prediction and found satisfactory. Further, the molecular docking of all the ferulic acid amide derivatives with human peptide deformylase (Homo sapiens; HsPDF; PDB ID: 5G5K) have been carried which confirmed the inhibition of HsPDF and the data were also found in line with the previously reported experimental results by our research group. Results of docking studies manifest Va-Vg (containing acridine moiety) as the top five HsPDF inhibitors as most potent efficacious and selective drugs in the form of docking score as compared to their parent molecule. The in vitro and in silico studies performed for these proposed inhibitors showed the potentials to become a vital anticancer candidate and in future possibly be either used alone or in combination with known existing drugs which can together act synergistically more effectively to treat different type of cancer.