Synthesis of tetracyclic benzodioxins as potential antitumour agents.
We report the synthesis of five new tetracyclic benzodioxins, from reaction of 1,2-naphthalenediol, 7,8-dihydroxyquinoline or 7,8-dihydroxyisoquinoline with isopropyl 2-chloro-3-nitrobenzoate. Mixtures of isomeric esters were obtained which were separated by conventional flash silica chromatography or preparative HPLC and fully characterized by NMR. Ester hydrolysis and amide formation afforded the target carboxamides 7-9, 11 and 12. The biological activities of the benzodioxins broadly paralleled those of the corresponding phenazines. A tetracyclic pyrido derivative was the most cytotoxic, with an IC50 of 0.11 microM in P388 leukaemia cell culture, but did not represent a significant improvement over a number of 9-substituted tricyclic phenazines.
Spicer
J A
JA
Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, New Zealand. j.spicer@auckland.ac.nz
Denny
W A
WA
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004147:Dioxins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure
D000970:Antineoplastic Agents; D004147:Dioxins