In silico inhibitory activities of flavonoid and curcumin derivatives against GP IIb/IIIa receptor

Abstract

Background: Over the past 15 years, thrombosis has been one of the most common causes of death. Current antiplatelet therapies could limit the morbidity and mortality from thromboembolic diseases, but they still have side effects such as uncontrolled bleeding, and patients’ intolerance. Therefore, finding new antiplatelet agents is an important goal in improving the treatment of thrombotic diseases. Objective: To design flavonoid and curcumin derivatives that inhibit the glycoprotein (GP) IIb/IIIa receptor, which plays an important role in platelet aggregation. Materials and Methods: In silico models were built to predict the biological activities of chemical compounds. These models were used in virtual screening, and new structures were designed from most promising molecules. Results: The 2D-QSAR and molecular docking models were developed with good predictability. From the virtual screening process, 16 curcumin and 29 flavonoid derivatives were obtained with potential activities on target protein. Two substances S4 and S35 were selected for structural optimization, and two new compounds with the greatest potential for further research were found. Conclusion: The study will contribute to the orientation of finding lead compounds capable of inhibiting the receptor GP IIb/IIIa, thereby shortening the time to search for new substances in the treatment of thrombotic diseases. Key words: Thrombosis, GP IIb/IIIa receptor, in silico, QSAR, molecular docking, flavonoid, curcumin.