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Indexed by:期刊论文

Date of Publication:2009-11-01

Journal:BIOORGANIC & MEDICINAL CHEMISTRY

Included Journals:SCIE、PubMed、Scopus

Volume:17

Issue:21

Page Number:7615-7621

ISSN No.:0968-0896

Key Words:Acenaphtho[1,2-b]pyrrole; Cell cycle; Apoptosis; DNA

Abstract:A family of 8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carboxylic acid derivatives were synthesized as a result of our efforts to modify a series of acenaphthopyrrole aromatic-heterocycle compounds that proved to be potent anticancer drugs. Among the derivatives, 3d (3-(dimethylamino-propylamino)-8-oxo-8H-acenaphtho-[1,2-b]pyrrole-9-carboxylic acid) and 3g (3-piperidine-8-oxo-8H-acenaphtho-[1,2-b]pyrrole-9-carboxylic acid) showed potential anticancer activity and different action mechanism from our previously reported compounds. UV-vis absorption, circular dichroism and viscosity measurement indicated that effect of both compounds on the advanced DNA conformation was different, although they could bind to DNA in the same way. Cell cycle analysis showed that 3d could induce S-phase arrest followed by apoptosis, while 3g induced apoptosis. The results seem to imply that different action mechanism could contribute to the dissimilitude of biological activities toward 3d and 3g. (C) 2009 Elsevier Ltd. All rights reserved.