Molecular Docking and ADMET Study of Spice‐Derived Potential Phytochemicals against Human DNA Topoisomerase III Alpha

Abstract

AbstractSmall phytochemicals play an important role in therapeutics hence potential molecules in different spices are screened using Lipinski's and Veber's rule. Pharmacodynamics studies are carried out against the cancer target, DNA topoisomerase III alpha. In silico ADMET (absorption, distribution, metabolism, excretion, toxicity) studies are done with these compounds. Lipinski's and Veber's rule indicates that all 10 small phytochemicals have the potential to behave as oral drug‐like molecules. A molecular docking study shows that shogoal, demethoxycurcumin, capsaicin, ellagic acid, 6‐paradol, 6‐gingerol, carnosic acid, and curcumin bind strongly with the cancer target: human DNA topoisomerase‐III alpha. In silico absorption, a study reveals that only cinnamic acid, allicin, alpha turmerone, cinnamyl acetate, and carnosic acid have more than 96% human intestinal absorption, but only alpha turmerone can cross both the blood–brain barrier and central nervous system. In silico phase‐I, the metabolism study shows 6‐paradol and carnosic acid as substrates for cytochrome 450 enzyme (CYP450 3A4) and curcumin and dillapiol as inhibitors for CYP 450 2D6. Overall the study concludes that small phytochemicals present in different spices have the potential to be proposed as oral anti‐cancer drugs against cancer targets DNA topoisomerase III alpha.