An In Silico Study of the Epithelial Anticancer Activity of Caffeine Derivatives by using MIA-QSAR methods and Molecular Docking

Epithelial tumors are a type of cancers that eccure in epithelial cells in different part of the body and the most common of these is epithelial skin cancer, a malignant neoplasm of skin epithelial cells which is four times more common than other type of skin cancer [1]. Up to now, many studies on the mechanisms of antitumor initiating and antitumor promoting properties of potent drugs are currently being suggested for the prevention of skin cancer and other epithelial cancers in humans [2]. Caffeine is one of these compounds. Caffeine (1,3,7 trimethylxanthine) is an alkaloid compound belonging to the xanthine group. it contains in its composition nitrogen, oxygen, hydrogen and carbon [3]. In this study, inhibition activity of some caffeine derivatives (with specific amount of ICT50) against epithelial cancer, were studied by QSAR modeling and using application of pixel selection to predict the biological activity of caffeine and comparison with experimental data. In silico methods, such as quantitative structure activity relationship (QSAR), molecular docking and pharmacophore modelling by decreasing the time and cost of drug discovery play a significant role in the field of drug design and development [4].The QSAR model showed satisfactory output validation parameters, which made the model acceptable, and molecular docking simulation were developed for considering interaction of selected caffeine derivatives with their reseptors such as Chk1 and combination between their binding free energies. MIA-QSAR modeling and molecular docking studies showed valuable result that can help pharmaceutical researchs to design and synthesis new compounds with more epithelial anticancer activity.