Diacridines, bifunctional intercalators. Chemistry and antitumor activity. 1978

T K Chen, and R Fico, and E S Canellakis

The synthesis and the characterization of a number of diacridines connected through the 9-amino position of the acridine rings by alkyl chains of varying lengths and with various substituents on the acridine ring are described. An interesting chemical property has been noted; whereas the 3-amino monoacridines cannot form stable dihydrochloride salts, the corresponding diacridines can form stable trihydrochloride salts. The biological activity of the diacridines encompasses a broad spectrum of action. Their antitumor activity (% ILS) and their toxicity have been correlated with their biological actions. The % ILS, as measured by inhibition of growth of P-388 ascites cells in BDF/1 mice, shows no significant correlation with their ability to inhibit the growth of P-388 cells in culture (I50). The toxicity of the diacridines does not correlate with the inhibition of DNA or RNA synthesis, the uptake of the diacridines by P-388 cells, or with % ILS. The only significant correlation that has been found to date between the antitumor effectiveness of the diacridines and their effects on intact cells occurs between % ILS and cell agglutination. These results emphasize that caution should be used in attributing the "antitumor activity" of a single compound or of a small number of congeners of a given chemical structure to a particular site of biological inhibition. Furthermore, the results suggest that effective antitumor drugs are those that affect the host-tumor interaction and that the toxicity of the drugs may not be essential to their antitumor properties.

UI MeSH Term Description Entries
D008223 Lymphoma A general term for various neoplastic diseases of the lymphoid tissue. Germinoblastoma,Lymphoma, Malignant,Reticulolymphosarcoma,Sarcoma, Germinoblastic,Germinoblastic Sarcoma,Germinoblastic Sarcomas,Germinoblastomas,Lymphomas,Lymphomas, Malignant,Malignant Lymphoma,Malignant Lymphomas,Reticulolymphosarcomas,Sarcomas, Germinoblastic
D008811 Mice, Inbred DBA An inbred strain of mouse. Specific substrains are used in a variety of areas of BIOMEDICAL RESEARCH such as DBA/1J, which is used as a model for RHEUMATOID ARTHRITIS. Mice, DBA,Mouse, DBA,Mouse, Inbred DBA,DBA Mice,DBA Mice, Inbred,DBA Mouse,DBA Mouse, Inbred,Inbred DBA Mice,Inbred DBA Mouse
D009374 Neoplasms, Experimental Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms. Experimental Neoplasms,Experimental Neoplasm,Neoplasm, Experimental
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D002621 Chemistry A basic science concerned with the composition, structure, and properties of matter; and the reactions that occur between substances and the associated energy exchange.
D000166 Acridines Compounds that include the structure of acridine. Acridine
D000371 Agglutination The clumping together of suspended material resulting from the action of AGGLUTININS.
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D012334 RNA, Neoplasm RNA present in neoplastic tissue. Neoplasm RNA

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