NDLI: Relationship between the pharmacological activity of antitumor drugs Ametantrone and mitoxantrone (Novatrone) and their ability to condense nucleic acids.

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Relationship between the pharmacological activity of antitumor drugs Ametantrone and mitoxantrone (Novatrone) and their ability to condense nucleic acids.

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Relationship between the pharmacological activity of antitumor drugs Ametantrone and mitoxantrone (Novatrone) and their ability to condense nucleic acids.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Darzynkiewicz, Z. Kapuscinski, J.
Abstract	Ametantrone (HAQ) and mitoxantrone (DHAQ) are structurally similar antitumor drugs of the anthracenedione class. The cytostatic, cytotoxic, and antitumor activities of these drugs are different, with DHAQ being 10-100 times more potent, per molar basis. Both drugs are strong intercalators and intercalative modes of binding are suspected as relevant to their pharmacological activity. No significant differences, however, that could explain the differences in pharmacological activity are observed in their intercalative properties with respect to base specificity and binding affinity. A correlation, however, is evident between their potency and ability to condense nucleic acids inasmuch as DHAQ condenses nucleic acids at concentrations that are lower by a factor of 5-40 than those of HAQ and these effects can be observed at their pharmacological concentrations. The condensation is base- and sugar-specific and the long purine sequences of single-stranded RNA are the most sensitive. Electron microscopy of L1210 cells exposed a short time (90 min) to 0.21-21 microM DHAQ reveals segregation of nucleoli; the segregated granular portion shows increased electron opacity. In some preparations patchy areas of nuclear chromatin characterized by increased electron opacity can be seen. The results are compatible with the possibility that pharmacological effects of these antitumor drugs could involve condensation of nucleic acids, primarily of RNA in nucleoli.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	17
Volume Number	83
Language	English
Publisher	National Academy of Sciences
Publisher Date	1986-10-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Anthraquinones Pharmacology Antineoplastic Agents Intercalating Agents Nucleic Acid Conformation Drug Effects Animals Leukemia L1210 Drug Therapy Mice Microscopy, Electron Mitoxantrone Structure-Activity Relationship Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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