I. Robertson, W. Denny, B. Baguley
Sep 1, 1980
Citations
0
Influential Citations
17
Citations
Quality indicators
Journal
European journal of cancer
Abstract
Abstract A series of 9 -anilinoacridine derivatives, substituted in the anilino-ring, has been tested in a simple bacteriophage T 4 inhibition assay. Corresponding derivatives of 9 -anilino- 3 -aminoacridine and 9 -anilino- 3 , 6 -diaminoacridine have also been tested to provide a series of compounds with a wide range of DNA binding characteristics. Anti-tumour assays using the murine L 1210 leukaemia system have also been carried out and the results compared in terms of various physicochemical parameters. When biological activity is expressed as a function of DNA binding (estimated using an ethidium displacement assay) and molar refractivity values of the anilino-substituents, two conclusions can be made. Firstly, there is a requirement for a minimum degree of DNA binding in each system. Above this minimum, biological activity is only slightly altered by the magnitude of DNA binding. Secondly, anilino-substituents of smail size or polarisability are necessary for optimal activity in the phage system, whereas substituents of larger size or polarisability (e.g., methanesulphonamide) are necessary for optimal activity in the L 1210 leukaemia system. Thus the acridine moiety of these compounds plays the major role in DNA binding, whereas, the anilino-moiety may determine the biological selectivity.