Tautomers of styrylquinoline derivatives containing a methoxy substituent:Computation of their population in aqueous solution and their interaction with RSV integrase catalytic core

8-Hydroxy-2-[2-(3-hydroxy-4-methoxyphenyl)ethenyl]-7-quinoline carboxylic a cid and 8-hydroxy-2-[2-(3-methoxy-4-hydroxyphenyl)ethenyl]-7-quinoline carb oxylic acid inhibit the processing and strand transfer reactions catalyzed by HIV-1 integrase with an IC50 Of 2 mu M. Some of their spectral propertie s are briefly reported. Their fluorescence is so weak that it is of no use in an experimental determination of the binding to the protein and we resor ted to computer simulation. Both styrylquinoline derivatives, in their mono anionic form, have several dozens of tautomers and each of these forms has four planar rotamers. In this work computer simulations have been performed to determine which tautomer is the most abundant in aqueous solution and w hich binds to the Rous sarcoma virus (RSV) integrase catalytic core. As the substituents on the quinoline moiety are the same as on salicylic acid, th e energies of hydroxy benzoic acid tautomers were also computed both in vac uo and embedded in a continuous medium which had the dielectric constant of bulk water, using the recent CPCM technique. The CPCM method was then appl ied to the two integrase inhibitors to estimate the tautomer population in water. The binding site of the compounds on the RSV integrase catalytic cor e was determined through a docking protocol, consisting of coupling a grid search method with full energy minimization. The designed method is a way l eading to identification of potent integrase inhibitors using in silico exp eriments.