Selective Antimetastatic Triazenes: A Quantitative Approach

Abstract

AbstractQuantitative structure‐activity relationships have been formulated examining a series of para substituted phenyldimethyl‐triazenes for their differential effects on the subcutaneous growth of Lewis lung carcinoma and on the formation of its pulmonary metastases in mice. When the data were expressed as log 1/C, the QSAR obtained for toxicity as well as for the effects on primary tumor and metastases showed a similar dependency on the physicochemical constant chosen. Since drug potency expressed as log 1/C is obtained at the expenses of different toxicities for the tumor bearing host, drug activity was also expressed as the effect obtained at maximum tolerated drug dosages (log T/C). The QSAR resulting from the expression of the data as log T/C showed a dissociation between the effects on primary tumor as compared with those on metastases, quantitatively evidencing the observed selective antimetastatic properties of these substances. Aryldimethyltriazenes more active against metastases could be theoretically obtained for values of logP outside the range presently considered.