A Novel Synthesis of Benzo[c]phenanthridine Skeleton and Biological Evaluation of Isoquinoline Derivatives

• Published in: Chemical & pharmaceutical bulletin Vol. 47; no. 6; pp. 900 - 902
• Main Authors: CHO, Won-Jea, PARK, Myun-Ji, IMANISHI, Takeshi, CHUNG, Byung-Ho
• Format: Journal Article
• Language: English
• Published: TOKYO The Pharmaceutical Society of Japan 01.06.1999; Pharmaceutical Soc Japan; Maruzen; Japan Science and Technology Agency
• Subjects: Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; antitumor activity; benzo[c]phenanthridine; Biological and medical sciences; Cell Survival - drug effects; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; Drug Screening Assays, Antitumor; General aspects; Humans; indenoisoquinoline; Isoquinolines - chemical synthesis; Isoquinolines - pharmacology; Life Sciences & Biomedicine; Medical sciences; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Phenanthridines - chemical synthesis; Phenanthridines - pharmacology; Physical Sciences; radical cyclization; Science & Technology; Tumor Cells, Cultured; indenoisoquinoline; radical cyclization; ASSAY; benzo[c]phenanthridine; antitumor activity; ALKALOIDS; Antineoplastic agent; Human; Nitrogen heterocycle; Lactam; Cytotoxicity; Tetracyclic compound; In vitro; Free radical reaction; Cell line; Cyclization; Structure activity relation; Bicyclic compound; Aromatic compound; Chemical synthesis; Tumor cell
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.47.900

Benzo[c]phenanthridine skeleton was synthesized from easily available starting N-methyl-o-toluamide 2 and o-methylbenzonitrile 5 in 7 steps. Radical cyclization of styrene 10 afforded 6, 11-dimethyl-6, 11 -dihydro-5H-in-deno[1, 2-c]isoquinolin-5-one 13. Most 3-arylisoquinolines have displayed strong activities against human tumor cell lines. Especially, indenoisoquinolinone 13 exhibited excellent cytotoxicity (IC50=0.002 μg/ml; HCT 15).