QSAR analysis of polyamine transport inhibitors in L1210 cells

Purpose: In this paper, the authors attempt to construct a mathematical model to correlate the biological activities of 63 polyamine transport inhibitors in L1210 cells with their physicochemical parameters. Method: The inhibitory constants (K-i) were obtained from the published work of Bergeron ct al. Non-weighted least square method was used in deriving the regression equations with a BMDP program. An AMI subroutine of the HyperChem program was used to optimize the geometry and calculate the molecular dipole moments and the distance between two terminal amino groups. A CQSAR program was used to calculate Clog P (oct./w.). Results: A good correlation (r(2)=0.81) was obtained by using a five-parameter equation including the distance between two terminal amino groups (d), the number of cationic charge (Charge), molecular weight (MW), dipole moment (mu), and hydrogen bond forming ability (Hb). Conclusion: This model accounts for 81% of the variance in the data and can be used to estimate transport-inhibitory activity of many other polyamine analogues. It gives some quantitative information about the relationship between the polyamine analogues function as transport inhibitors and their molecular structures.