Xia C Q, Yang J J, Ren S, Lien E J
Department of Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles 90033, USA.
J Drug Target. 1998;6(1):65-77. doi: 10.3109/10611869808997882.
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.
The inhibitory constants (Ki) were obtained from the published work of Bergeron et al. Non-weighted least square method was used in deriving the regression equations with a BMDP program. An AM1 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.).
A good correlation (r2 = 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).
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.
