Antitumour activity of substituted 9-anilinoacridines—Comparison of in vivo and in vitro testing systems

The search for derivatives of 9-anilinoacridine by Cain and co-workers [1] using murine L1210 leukemia as a test system, culminated in the synthesis of 4′-(9-acridinylamino)methanesulphon-m-anisidide (m-AMSA, NSC 249,992), which is now undergoing clinical trial. The steps on the development of this and related compounds have been retraced using L1210 cells in culture. The results obtained with the in vitro system have indicated m-AMSA to have an appropriate choice of substituents for optimal activity, in agreement with results of the corresponding in vivo test system. m-AMSA causes a 50% inhibition of L1210 cell growth in culture under standard conditions (3 day cultures) at 3.5 × 10⁻⁸ M. Three compounds in which the substituent on the anilino ring contains a second benzene ring are highly active in culture, one being 100-fold more active than m-AMSA.