S. Cohen, K. L. Yielding
Jul 1, 1965
Citations
1
Influential Citations
170
Citations
Quality indicators
Journal
The Journal of biological chemistry
Abstract
The observations made by Irvin, Irvin, and Parker in 1949 (1) that quinoline and acridine antimalarial compounds can interact with nucleic acids in vitro suggested a possible mechanism by which these agents might interfere with cellular processes in malarial parasites. While the nature and consequences of the interaction between various acridine derivatives and deoxyribonucleic acid have since been the subject of much investigation (a-lo), complex formation between quinolines and nucleic acids has received relatively scant attention. Recently, however, there has been a renewal of interest in the latter type of interaction, and more specifically in the binding of chloroquine, a 4-aminoquinoline which is widely used in clinical medicine, to DNA (9, 11). Chloroquine (7-chloro-4-(4-dieth~~lamino-l-methylbutylamino)quinoline) is one of a large series of quinolines in which antimalarial activity was studied extensively during and immediately following World War II (12, 13). Early work indicated that in dilute aqueous solutions at physiological pH chloroquine exists as a doubly protonated cation (14), and that it is this molecular form that binds to nucleic acids (15). Subsequently, it has been observed that certain of the biological properties of DNA are markedly altered by its interaction with chloroquine, and that such complex formation can (a) inhibit enzymic depolymerization of DNA (9), (b) reduce its bacterial t,ransforming ability (II), and (c) interfere with its function as a primer for the DNA-dependent DNA and RNA polymerase reactions (16). The ability of chloroquine to affect the functioning of DNA in biological systems suggests that this compound might be useful in studying the mechanisms involved in certain DNA-dependent cellular processes. The present investigations concern the specific molecular nature of the chloroquine-DNA interaction, and examine the structural requirements for the participating molecules by the use of various nucleic acid polymers and chloroquine analogues. Preliminary reports of certain of these observations have been published elsewhere (17, 18).