Cancer chemotherapy: drug combination and multiple modality treatment.

Research has provided many antitumour agents which show varying degrees of effectness against both experimental animal and human cancers. Successful selection of drugs for use in combination can increase antitumour effectiveness. Combination toxicity indices can assist in selecting potentially useful drug combinations.

Potential antitumor agents. 19. Multiply substituted 4'-(9-acridinylamino)methanesulfonanilides.

A series of 42 multiply substituted 4'-(9-acridinylamino)methanesulfonanilides has been prepared and evaluated in the L1210 system. In addition to biologic activity changes resulting from altered agent lipophilic-hydrophilic balance variants containing both acridine 4-CH3 and 3-NH2, NHCOCH3 or NO2 substituents have reduced activity. Variants 3,6-disubstituted, using functions of differing electronic character, have depressed activity, suggesting that there is limited site bulk tolerance.

Potential antitumor agents. 17. 9-Anilino-10-methylacridinium salts.

9-Anilino-10-methylacridinium salts result from reaction of substituted anilines and 9-chloro-10-methylacridinium salts in turn prepared from the 10-methyl-9(10H)-acridones and SOCl2 or POCl3. Antileukemic (L1210) activities of the quaternary salts were uniformly depressed compared to their unquaternized counterparts. If drug-solvent partition properties (log P) of the cations were considered, log P-activity relationships were similar for both base and quaternary salt series.

Potential antitumor agents. 16.4'-(Acridin-9-ylamino)methanesulfonanilides.

The structure-antileukemic activity (L1210) relationships for sulfonanilide ring-substituted variants of 4'-(acridin-9-ylamino)methanesulfonanilides have been investigated. Electron-donor substituents are necessary for antileukemic activity and it is suggested that high electron density at the 6' position is associated with high activity. A 3'-OCH3 function markedly increases (2-8-fold) potency with a variety of acceptable acridine ring substituents.