Comparison of the binding of anthracycline derivatives to purified DNA and to cell nuclei

• Published in: Biochimica et biophysica acta Vol. 1036; no. 2; pp. 121 - 127
• Main Authors: Frezard, Frédéric, Garnier-Suillerot, Arlette
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 09.11.1990; Elsevier; North-Holland
• Subjects: Aclarubicin - analogs & derivatives; Aclarubicin - metabolism; Adriamycin; Anthracycline; Antibiotics, Antineoplastic - metabolism; Antineoplastic agents; Antineoplastic Agents - metabolism; Biological and medical sciences; Cell nucleus; Cell Nucleus - metabolism; Daunorubicin - metabolism; DNA; DNA - metabolism; Doxorubicin - analogs & derivatives; Doxorubicin - metabolism; Fluorescence; General aspects; Kinetics; Medical sciences; Molecular Structure; p Ka; Pharmacology. Drug treatments; Structure-Activity Relationship; Anthracycline; p K a; Adriamycin; DNA; Cell nucleus; Fluorescence; DNR; MDR; THP-ADR; ACM; ADR; Cell culture; Antibiotic; Purification; Molecular structure; Association constant; Molecular interaction; Anthracyclins; PK; Fluorescence spectrometry
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/0304-4165(90)90023-P

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 p K a 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 K 0 and K + of the respectively neutral form and once protonated form of the drugs to DNA were calculated. Using cell nuclei from K 562 cells, the amount of drug intercalated, ( C N) within the nuclei of K 562 cells and the amount of free drug ( C E) in the solution were determined at various pH values: measuring at the same pH values, a linear correlation occurred between K ∗ and C N C E .