QSAR ANALYSIS OF POLYAMINE TRANSPORT INHIBITORS IN L1210 CELLS

Purpose: In this paper, the authors attempt to construct a mathematica l model to correlate the biological activities of 63 polyamine transpo rt inhibitors in L1210 cells with their physicochemical parameters. Me thod: The inhibitory constants (K-i) were obtained from the published work of Bergeron ct al. Non-weighted least square method was used in d eriving the regression equations with a BMDP program. An AMI subroutin e of the HyperChem program was used to optimize the geometry and calcu late the molecular dipole moments and the distance between two termina l 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). Concl usion: This model accounts for 81% of the variance in the data and can be used to estimate transport-inhibitory activity of many other polya mine analogues. It gives some quantitative information about the relat ionship between the polyamine analogues function as transport inhibito rs and their molecular structures.