Эта работа опубликована в сборнике научных трудов «Естествознание и гуманизм» (2005 год, Том 2, выпуск 4), под редакцией проф., д.б.н. Ильинских Н.Н. Посмотреть титульный лист сборника

Resveratrol (3,5,4’-trihydroxy-trans-stilbene) is found in grapes, peanuts and other plants.  In addition to its cytotoxic, antifungal, antibacterial, and cardioprotective activities, resveratrol also inhibits cyclooxygenase-2 (COX2) activity.  COX2 is an inducible form of COX and its expression is affected by various stimuli such as mitogens, oncogenes, tumor promoters and growth factors.  At least 1 analogue (RSVL-2) has been shown to be a more potent inhibitor of EGF- or TPA-induced cell transformation compared to the parent compound, resveratrol.  In order to find more selective COX-2 inhibitors, 32 resveratrol derivatives were synthesized.  These analogues were used in molecular docking studies to identify potential candidates for inhibition of COX-2 activity.  For these docking (i.e., binding) studies, the CAChe 6.1 and Sybyl 7.1 computer software programs were used as a multiple approach to dock a chemical library.  The CAChe program uses Potential of Mean Force (PMF) and Sybyl 7.1 uses FlexX.  The docking of the resveratrol analogues into COX-2 (PDB code 4COX.pdb) active site was executed using different procedures, including rigid ligand into rigid protein, flexible ligand into rigid protein, flexible ligand into flexible protein, and flexible ligand into rigid protein with Amber.  Using these modeling systems, we identified several analogues that can function as COX-2 inhibitors with a higher potency than the parent compound, resveratrol.