Molecular dynamic simulation analysis on marine fungi compounds against EGFR and VEGFR-2 inhibitory activity in non-small cell lung cancer

Abstract

Introduction: According to International Agency for Research on Cancer (IARC), the number of lung cancer patients has reached 1.8 million lives, and 85% of the number contribute to non-small cell lung cancer. In the past years, research on targeted therapy has been developed due to its efficacy and a small number of side effects. Research on marine fungi compounds has not been explored to non-small cell lung cancer therapy. Methods: This research uses molecular dynamics simulation method to marine fungi compounds that have been docked to EGFR (FU0015, FU0051, FU0202) and VEGFR-2 (FU0033) as antiproliferative and antiangiogenetic agent by inhibition activity using AutoDock and AMBER at 300K and 310K temperature using EGFR (Gefitinib, Erlotinib, and Imatinib) and VEGFR-2 (Nicotinamide and Vatalanib) as reference standards. Results: Molecular dynamics results for EGFR inhibitors at 310K shows the best MMGBSA free energy and hydrogen occupancy in FU0051 (-43.72 kcal/mol; 98.80%) followed by FU0202 (-31.64 kcal/mol; 43.35%), and FU0015 (-15.55 kcal/mol; 3.35%). FU0033 fungi as a material for VEGFR-2 inhibitor shows higher MMGBSA free energy in comparison to its reference standards and low hydrogen occupancy (0.15%) at 310K. Conclusion:This research shows that FU0051 and FU0202 have potential to be an antiproliferative agent candidate, hence in vitro test should be obtained.