Potential antitumor agents. 26. Anionic congeners of the 9-anilinoacridines

Abstract

To investigate the possible importance of small levels of sulfonamide anion in the antileukemia (L1210) 4'-(9-acridinylamino)methanesulfonanilides, an anionic derivative was prepared, in which -COOH replaced -NHSO2CH3, and shown to have experimental antitumor activity. Analogue synthesis and evaluation show that acceptable placement of the carboxylate function on the 9-anilino ring is restricted to the 1'-position. While the 1'-COOH and 1'-(CH2)2COOH analogues proved active, the intermediate acetate variant (1'-CH2COOH) was inactive. There were marked differences in the effects of added acridine ring substituents, on biologic activity, depending on the function attached to the 9-anilino ring (1'-NHSO2CH3 or 1'-COOH). Consideration of the vector components of possible drug-binding forces, acting on a DNA-intercalated agent, suggests that there may be low-energy barriers to two-dimensional reorientation of a planar, intercalated chromophore in relation to the neighboring purine-pyrimidine base pairs. It is proposed that site forces from an added substituent could lead to modified DNA-binding orientations. Observed acridine-ring substituent effects on biologic activity would then depend on the 9-anilino ring function (1'-NHSO2CH3, 1'-COOH) employed.

Potential antitumor agents. 28. Deoxyribonucleic acid polyintercalating agents

“…The bulk of these intermediates has been previously prepared, by somewhat more cumbersome procedures, and recorded physical constants64,66 were in good agreement with those observed. Not formerly recorded were l,7-bis(2-nitrophenoxy)heptane, mp [60][61] 1.4-Bis(2-acetamido-5-nitrophenoxy)butane. To a stirred, ice-water-cooled suspension of 2-hydroxy-4-nitroacetanilide (10 g, 0.053 mol) in DMF (8 mL), NaH (1.22 g, 0.053 mol) was added as permitted by the resulting effervescence.…”

Enhanced killing of mammalian cells by radiation combined with m-AMSA

“…that therapists hope will extend the range of cancer chemotherapeutic drugs are the 9-anilinoacridines developed by Cain and his co-workers (Denny et al, 1978, and references therein). Reversibility of myelosuppression and limited other side effects are attractive features of m-AMSA (4'-[9 -acridinylamino] -methanesulphon -manisidide) the derivative on which attention has been focused initially.…”

DNA‐Binding and Anticancer Activity of Pyrene‐Imidazolium Derivatives

“…In addition, the presence of aromatic planar groups is key to allow p-p stacking interactions with the DNA nitrogen bases, occurring in intercalation or top stacking. [4,5] Very often the two groups are present in one molecule: the aromatic ring can be positively charged, [6] positively charged residues can be appended on side groups, [7,8] or a positive charge is conferred by metal ions in complexes of aromatic ligands. [9,10] In this context, it has been recently reported that a dicationic pyrene-imidazolium derivative, in which two pyreneimidazolium units are bridged by a C 1 linker, is able to selectively bind to G-quadruplex (G4) DNA, preferring it to double-stranded (ds) DNA.…”