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Studies on the Mechanisms of Action of Various Phthalanilide Derivatives by Cross-Resistance and Tissue Culture^*

( Divisions of Experimental and Clinical Chemotherapy, Sloan-Kettering Institute for Cancer Research, and Cornell University Medical College, New York, New York)

In lines of leukemias P815 and P388 resistance has been developed to three Wander derivatives of different structures. Cross-resistance between the various members of this series has been studied. The lack of cross-resistance between certain of these derivatives suggests different mechanisms of action.

In tissue culture with cells of leukemia P815Y there appears to be reasonably good correlation between in vivo and in vitro antileukemic activity. The Wander compounds so far studied are absorbed rapidly by the cells, but it takes 48–72 hours for the inhibitory effect to become evident. This technic would appear useful for screening and studying mechanisms of action of the Wander compounds.

^* These studies were supported in part by Research Contract SA-43-ph-2445, Cancer Chemotherapy National Service Center of the United States Public Health Service, by Grant ACS T 45 from the American Cancer Society, and by the United Leukemia Fund.

These compounds were synthesized by the Dr. A. Wander AG of Berne, Switzerland, and kindly supplied by the Cancer Chemotherapy National Service Center of the National Cancer Institute.