Theoretical Study of Isoindolines to Identify them as Cyclooxygenase-1 and -2 Inhibitors by Docking Simulations

This work describes a theoretical study of two series of isoindolines 1(a-h) and 2(a-h) as possible COX-1 and COX-2 inhibitors by Docking method. Whereas, the same study was carried out for isoindolilamides 3-5, which have shown anti-inflammatory and analgesic effects, as well as ibuprofen 6 and dihydrodimethylben- zofuran 7, which are well-known as excellent anti-inflammatory. Compounds 6 and 7 were used to identify the active sites on these two enzymes and compared with those obtained from isoindolines under docking studies. The analysis of Docking results show that compounds 1(a-h) and 2(a-h) could inhibit both cyclooxygenases (COXs), due to the fact that they act in the same region as those taken as reference (3-7) make several interactions with the amino acid residues that conform the active sites of both COXs. ΔG values were obtained for all compounds, they are between -9.87 and -6.65 (Kcal/mol, COX-1) and -10.96 and -6.28 (Kcal/mol, COX-2), being COX-1-1h and COX-2-1h complexes more stable. Therefore, Kd (�� M) values were obtained, they are in the range of 0.06 and 13.5 in COX-1 and finally the values between 0.01 and 24.7 in COX-2, where 1h shows more affinity to both COX-1 and COX-2.