Synthesis of 9,9-dialkyl-4,5-diazafluorene derivatives and their structure-activity relationships toward human carcinoma cell lines

Qiwei Wang, Marcus Chun Wah Yuen, Guo Liang Lu, Cheuk Lam Ho, Gui Jiang Zhou, Oi Mei Keung, Kim Hung Lam, Roberto Gambari, Xiaoming Tao, Raymond Siu Ming Wong, See Wai Tong, Kit Wah Chan, Fung Yi Lau, Filly Cheung, Gregory Yin Ming Cheng, Chung Hin Chui, Wai Yeung Wong

Research output: Journal article publicationJournal articleAcademic researchpeer-review

18 Citations (Scopus)

Abstract

A homologous set of 9,9-dialkyl-4,5-diazafluorene compounds were prepared by alkylation of 4,5-diazafluorene with the appropriate alkyl bromide and under basic conditions. The structures of these simple organic compounds were confirmed by spectroscopic techniques (FTIR, NMR, and FABMS). Their biological effects toward a panel of human carcinoma cells, including Hep3B hepatocellular carcinoma, MDAMB-231 breast carcinoma, and SKHep-1 hepatoma cells, were investigated; a structure-activity correlation was established with respect to the length of the alkyl chain and the fluorene ring structure. The relationship between the mean potency [log(1/IC50)] and alkyl chain length was systematically studied. The results show that compounds with butyl, hexyl, and octyl chains exhibit good growth inhibitory effects toward these three human carcinoma cell lines, and the 9,9-dihexyl-4,5-diazafluorene further exhibits antitumor activity in athymic nude mice Hep3B xenograft models. For the structurally related dialkylfluorenes that lack the diaza functionality, in vitro cytotoxicity was not observed at clinically relevant concentrations. KGaA, Weinheim.
Original languageEnglish
Pages (from-to)559-566
Number of pages8
JournalChemMedChem
Volume5
Issue number4
DOIs
Publication statusPublished - 6 Apr 2010

Keywords

  • Cytotoxicity
  • Diazafluorenes
  • Hepatoma
  • Synthesis
  • Xenografts

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

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