EGFR Kinase domain is a crucial role player cell surface receptor protein activated by specific binding of its ligand like EGFR. Importance of this protein as a therapeutically important drug target towards treating various cancer types has been proven elsewhere in previous literature. In this present study, we have designed a novel series of five compounds and computationally evaluated their potential to act as inhibitors of EGFR kinase domain towards anti-cancer activity. Our docking study shows compounds have the potential to dock into the active site of the EGFR Kinase domain with a binding energy in a range of -5.46 to - 7.32 Kcal/mol, Among all the compounds, compound 2 was found to be the lead like molecule with the binding energy of -7.32 kcal/mol with predicted IC50 value of 4.33 micro molar level. Molecular dynamic simulation studies for this compound 2 in complex with EGFR kinase domain has revealed several interesting molecular interactions with some of the important residues present at the active binding site of EGFR Kinase domain. Conclusively, novel designed compound 2 of the present study have shown promising anti-cancer potential worth considering for further evaluations.

The Mentha genus includes several species such as Mentha rotundifolia L., which is widely distributed around the Mediterranean basin, America and in western Asia.  The plant is recommended in folk medicine for the treatment of various diseases. It has also been used to discover biomolecules that have significant beneficial effects with fewer side effects. Mentha rotundifolia (L) leaves are potential as an antihypertensive cause of terpenes which contain in them. 36 different terpenes and terpenoids have been identified and selected from this plant.  This study evaluated the mechanism of phytoconstituents from the above plant in the inhibition of angiotensin-converting enzyme-related carboxypeptidase (ACE2) with molecular docking. Selected ligands were docked on the receptor (PDB ID: 1R4L) using Auto Dock Vina and analysed by PyMol. 2D and 3D structures of compounds were drawn by the Chem Draw program. The standard drug that has been taken for the study, lisinopril, has shown a binding affinity of -7.8 Kcal/mol. Calacorene, one of the terpenes present in the plant, has interacted with Phe274, Asp367, Glu406, Thr445, Thr371 residues of protein and produced a docking score similar to that of the standard drug Lisinopril. In the light of the results obtained, the plant studied is promising as a source of natural hypotensive agent that can be further developed as a lead molecule.