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Alkyl‐linked diquinolines are monofunctional AT‐selective DNA‐intercalating agents
Author(s) -
McFadyen W.David,
Denny William A.,
Wakelin Laurence P.G.
Publication year - 1988
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(88)80006-1
Subject(s) - chemistry , intercalation (chemistry) , alkyl , selectivity , quinoline , ionic strength , dna , heptane , stereochemistry , ligand (biochemistry) , affinities , titration , medicinal chemistry , inorganic chemistry , organic chemistry , receptor , biochemistry , aqueous solution , catalysis
The binding of a homologous series of alkyl‐linked 4‐aminodiquinolines to circular and linear DNAs was studied using viscometric titrations and equilibrium dialysis. The compounds are monofunctional intercalators with the capacity for intercalative binding reaching a peak for the heptane homologue. They show marked AT‐base pair selectivity, which suggests that the non‐intercalated quinoline ring may lie in the DNA minor groove. Affinities for calf thymus DNA increase as the alkyl chain is lengthened, falling in the range 6 to > 250 × 10 4 M −1 in a buffer of I 0.01. The association constant of the heptane diquinoline decreases with increasing ionic strength, 2.1 cations being released per bound dipositive ligand molecule. All the agents are growth inhibitory towards mouse leukemia cells in culture with IC 50 values in the range 0.06–18μM.