engleski

Calculation Procedures for Molecular Lipophilicity : a Comparative Study for Nine Dimers of 4-hydroxy-coumarins

The lipophilic character of compounds studied appears to be one of the most important parameters in the relations between structure and biological activity. The most frequently used n-octanol/water partition coefficient, P or its logarithm (log P), have important use in predicting transmembrane transport properties, protein binding and receptor affinity. The widespread application of lipophilicity to drug design explains the need for quick procedures to quantify molecular lipophilicity, particulary at the screening level. Recent reports have appeared on high HIV integrase inhibitory potency of certain coumarin dimers analogues. Previous studies showed that the active pharmacophore was consisted of a coumarin dimers containing an aryl substituent on the central linker methylene. Log P values for 9 dimers of 4-hydroxy-coumarin were calculated using three computer programs: Hyperchem 7.0 (based on atom contributions), KowWin (based on atom/fragment contributions) and CLOGP (based on fragmental contributions). The statistical analysis of log P values estimated by this programmes have shown better correlation between HYPERCHEM and CLOGP programme (r=0, 94), but mean values were very different: 2.709 for HYPERCHEM, 3.493 for KowWin and 4.759 for CLOGP. In our further work log P values of the nine dimers of 4-hydroxy-coumarins will be experimentally determinated.

lipophilicity; log P; HIV integrase; coumarin dimers; computer programs

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