Biomaterial Database

QSAR of acridines, III. Structure-activity relationship for antitumour imidazoacridinones and intercorrelations between in vivo and in vitro tests. 1996

Z Mazerska, and E Augustin, and J Dziegielewski, and M W Chołody, and J Konopa

Department of Pharmaceutical Technology and Biochemistry, Technical University of Gdańsk, Poland.

A study on quantitative relationships between the biological activity and physicochemical properties of antitumour 5-alkylaminoimidazoacridinone derivatives was carried out. The activity was based on the results of several in vitro tests as well as experimental antileukaemic therapy. The capacity factor, log k', determined by the reverse-phase HPLC method, was a measure of lipophilic properties. UV and NMR spectra of the compounds were employed to describe electronic parameters. Values of steric descriptors were calculated as topological indexes. Results obtained by means of principal component analysis (PCA) allow us to group biological tests into two subsets: the lipophilicity-dependent and lipophilicity-independent test groups. The highest intercorrelation, R = 0.92, was shown between the optimal dose, pOD, determined in leukaemia P388-bearing mice and cytotoxicity expressed as pEC50 in leukaemia cells. The equation describing this relationship could be applied to predict the therapeutic doses of imidazoacridinone derivatives which would be effective in experimental antileukaemic therapy. The quantitative structure-activity relationship (QSAR) study showed that lipophilic properties significantly influence cytotoxicity, pEC50, and antileukaemic potency, pOD, only in the case of 8-hydroxy analogues of imidazoacridinones, whereas the activity of the remaining derivatives is very low and does not depend on lipophilicity. Electronic resonance properties seem to influence this specific impact of lipophilicity on the biological activity of 8-hydroxy derivatives. Hence, it may be possible to improve the antitumour activity of 8-hydroxyimidazoacridinones by obtaining more hydrophilic derivatives, up to the optimal value of the lipophilic parameter.

UI	MeSH Term	Description	Entries
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
D002470	Cell Survival	The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.	Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D000585	Aminacrine	A highly fluorescent anti-infective dye used clinically as a topical antiseptic and experimentally as a mutagen, due to its interaction with DNA. It is also used as an intracellular pH indicator.	9-Aminoacridine,Acridinamine,Aminacrine Hydrochloride,Aminoacridine,Aminoacridine Hydrochloride,Aminopt,Mykocert,9 Aminoacridine,Hydrochloride, Aminacrine,Hydrochloride, Aminoacridine
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
D012995	Solubility	The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)	Solubilities
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D016923	Cell Death	The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.	Death, Cell
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus