Towards targeting EGFR and COX-2 inhibitors: comprehensive computational studies on the role of chlorine group in novel thienyl-pyrazoline derivative

Abstract

To enhance the effectiveness of chemotherapy and overcome resistance, scientists must develop novel drugs or scaffolds that have a combined effect, such as the inhibition of EGFR and COX-2. This research employed virtual screening techniques, such as docking, and dynamics simulation, to predict chlorinated thienyl-pyrazoline derivatives that inhibit these proteins. The study proposed eleven (11) ligands with binding energies ranging from −7.8 kcal/mol to −8.7 kcal/mol for EGFR and −6.4 kcal/mol to −8.4 kcal/mol for COX-2. Ligands P1 and P11 exhibited the highest binding affinity for both proteins. The results of RMSD, RMSF, RoG, SASA the number of hydrogen bonds, and BAR free binding energy demonstrated the good stability of ligands P1 and P11 when binding to both proteins over 180 ns simulations. In addition, the absorption, distribution, metabolism, excretion, and toxicity properties of the selected ligands were assessed to predict their toxicity and drug likeliness. Based on the results, these compounds can be proposed for further synthesis and in vitro studies. Communicated by Ramaswamy H. Sarma