Antioxidant and Anti-Cancer Insights of Phyla Nodiflora Against Cox-2 Domains Through Conformational Molecular Dynamic Simulations

Abstract

Cancer is one of the most mortal illnesses in the world. Cancer patients showed elevated levels of COX-2 enzyme and prostaglandin. This points towards the potential target of this enzyme in order to inhibit its enzymatic activity and thus lower prostaglandin. Phyla nodiflora was also reported to trigger apoptosis and cell cycle progression in MCF-7 breast cancer cells with augmented expression of tumorigenesis-inducing transcription factors. The increased antioxidant activity in Ehrlich-Lettre ascites carcinoma (EAC-bearing) mice may be responsible for anticancer activity. We decided to conduct experimental DPPH assays and in silico studies, including molecular docking, molecular dynamic simulation, drug-likeness, ADME, and toxicity, to find therapeutic agents to validate the anticancer and antioxidant activity of the plant. The antioxidant activity of the methanolic extract of the leaf was 42.69% when a 1mg dose of the leaf extract was used, while it increased to 64.49% when the dose of the leaf was increased to 7mg. Molecular docking shows that plant compounds like 8-methoxyluteolin (-8.8 kcal/mol), 8-methoxyapigenin (-8.3 kcal/mol), and 3-methylherbacetin (-9.1 kcal/mol) are ideal possible drug candidates since they have the highest binding affinities and follow Lipinski’s rule of five. Molecular dynamic simulation, RMSD, and RMSF values show that they have good binding interaction with the receptor and are stable, hence showing that these compounds may act as novel therapeutic agents against cancers.