COMPARISON OF THE BINDING OF ANTHRACYCLINE DERIVATIVES TO PURIFIED DNA AND TO CELL-NUCLEI

Fluorescence method was used to study the interactions of anthracyclines with purified DNA and with cell nuclei at 37°C, at pH ranging from 6.8 to 8. Four anthracyclines were used; adriamycin (ADR), 4′-o-tetrahydropyranyladriamycin (THP-ADR), daunorubicin (DNR) and aclacinomycin (ACM). The values of pKa of deprotonation of these four drugs in the pH range 6.5-8.5 are 8.4, 7.7, 8.4 and 7.0 for ADR, THP-ADR, DNR and ACM, respectively. The overall binding constants K* of these four drugs to purified DNA was determined at various pH values. The binding constants K0 and K+ of the respectively neutral form and once protonated form of the drugs to DNA were calculated. Using cell nuclei from K562 cells, the amount of drug intercalated, (CN) within the nuclei of K562 cells and the amount of free drug (CE) in the solution were determined at various pH values: measuring at the same pH values, a linear correlation occurred between K* and CN CE. © 1990.