Synthesis and evaluation as potential anticancer agents of novel tetracyclic indenoquinoline derivatives.
We report the synthesis and evaluation as potential anticancer agents of a series of tetracyclic indenoquinolines. The compounds, which are obtained through the photoisomerization of Diels-Alder adducts formed between purpurogallin derivatives and nitrosobenzene, have in vitro antiproliferative activities in the μM to nM range against breast (MCF-7), lung epithelial (A-549), and cervical (HeLa) adenocarcinoma cells. The cytotoxicities of several of the novel tetracycles are comparable to or better than that of camptothecin. A strong correlation between the activity of the compounds and their aromaticity and planarity was observed, suggesting a mode of action similar to that of topoisomerase poisons.
Department of Chemistry & Biochemistry, University of the Sciences in Philadelphia, 600 South Forty-Third Street, Philadelphia, PA 19104, USA.
Shubhashis
S
Chakrabarty
Michael S
MS
Croft
Melissa G
MG
Marko
Guillermo
G
Moyna
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D001567:Benzocycloheptenes / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D002166:Camptothecin / Q000737:chemistry / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D061565:Cycloaddition Reaction; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D009603:Nitroso Compounds / Q000737:chemistry; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity
D000970:Antineoplastic Agents; D001567:Benzocycloheptenes; D009603:Nitroso Compounds; D011804:Quinolines; C026133:purpurogallin; D002166:Camptothecin; C012456:nitrosobenzene