title: Synthesis of 9,9-dialkyl-4,5-diazafluorene derivatives and their structure-activity relationships toward human carcinoma cell lines.
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/IC(50))] 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.
authors.affiliation: Department of Chemistry and Centre for Advanced Luminescence Materials, Hong Kong Baptist University, Waterloo Road, Kowloon Tong, Hong Kong, PR China.
authors.forename: Qiwei
authors.initials: Q
authors.lastname: Wang
authors.forename: Marcus Chun-Wah
authors.initials: MC
authors.lastname: Yuen
authors.forename: Guo-Liang
authors.initials: GL
authors.lastname: Lu
authors.forename: Cheuk-Lam
authors.initials: CL
authors.lastname: Ho
authors.forename: Gui-Jiang
authors.initials: GJ
authors.lastname: Zhou
authors.forename: Oi-Mei
authors.initials: OM
authors.lastname: Keung
authors.forename: Kim-Hung
authors.initials: KH
authors.lastname: Lam
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Tao
authors.forename: Raymond Siu-Ming
authors.initials: RS
authors.lastname: Wong
authors.forename: See-Wai
authors.initials: SW
authors.lastname: Tong
authors.forename: Kit-Wah
authors.initials: KW
authors.lastname: Chan
authors.forename: Fung-Yi
authors.initials: FY
authors.lastname: Lau
authors.forename: Filly
authors.initials: F
authors.lastname: Cheung
authors.forename: Gregory Yin-Ming
authors.initials: GY
authors.lastname: Cheng
authors.forename: Chung-Hin
authors.initials: CH
authors.lastname: Chui
authors.forename: Wai-Yeung
authors.initials: WY
authors.lastname: Wong
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D001943:Breast Neoplasms / Q000188:drug therapy; D002277:Carcinoma / Q000188:drug therapy*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D045744:Cell Line, Tumor; D005260:Female; D005449:Fluorenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy; D051379:Mice; D008819:Mice, Nude; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D005449:Fluorenes