Polycyclic aromatic compounds as anticancer agents: structure-activity relationships of chrysene and pyrene derivatives.
A large number of diamides and diamines were synthesized using 6-amino chrysene and 1-amino pyrene as starting materials. A structure activity study with cis-platinum as internal control against animal and human tumor lines was carried out in vitro. This study indicated that the in vitro cytotoxicity toward these lines depends on the functionality present in the molecules. The diamino compounds were found to be more potent than the diamides, and these were equally active irrespective of the end heterocyclic group, whereas the activity of the diamides was strongly dependent on the terminal unit. In general, the diamides containing chrysene as the chromophore were more active than those with a pyrene ring. The size of the end heterocyclic ring, along with the nature of the spacer connecting the polycyclic ring to the heterocyclic ring, seemed to affect the biological activity in certain cell lines. Hemolysis experiments on a lead compound established that it had activities similar to those described for membrane-stabilizing agents. This agent also demonstrated the capacity to produce differentiation in leukemia cell lines.
Banik
B K
BK
The University of Texas, M. D. Anderson Cancer Center, Department of Molecular Pathology, Houston 77030, USA. banik@solace.mdacc.tmc.edu
Becker
F F
FF
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D001835:Body Weight / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002911:Chrysenes / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D007267:Injections; D051379:Mice; D008819:Mice, Nude; D011084:Polycyclic Aromatic Hydrocarbons / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D011721:Pyrenes / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D015996:Survival Rate; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002911:Chrysenes; D011084:Polycyclic Aromatic Hydrocarbons; D011721:Pyrenes