Antitumor activity of diethynylfluorene derivatives of gold(I)

• Published in: Bioorganic & medicinal chemistry Vol. 17; no. 23; pp. 7872 - 7877
• Main Authors: Chui, Chung-Hin, Wong, Raymond Siu-Ming, Gambari, Roberto, Cheng, Gregory Yin-Ming, Yuen, Marcus Chun-Wah, Chan, Kit-Wah, Tong, See-Wai, Lau, Fung-Yi, Lai, Paul Bo-San, Lam, Kim-Hung, Ho, Cheuk-Lam, Kan, Chi-Wai, Leung, Kelvin Sze-Yin, Wong, Wai-Yeung
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01-12-2009; Elsevier
• Subjects: Alkynes; Animals; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biological and medical sciences; Cell Line, Tumor; Cell Survival - drug effects; Fluorenes - chemical synthesis; Fluorenes - chemistry; Fluorenes - pharmacology; Fluorenes derivatives; General aspects; Gold - chemistry; Gold - pharmacology; Gold(I) complexes; Human carcinoma cells; Humans; Magnetic Resonance Spectroscopy; Medical sciences; Mice; Mice, Nude; Neoplasms, Experimental - drug therapy; Nude mice model; Organometallic Compounds - chemistry; Organometallic Compounds - pharmacology; Pharmacology. Drug treatments; Reactive oxygen species; Spectrometry, Mass, Fast Atom Bombardment; Spectroscopy, Fourier Transform Infrared; Structure-Activity Relationship; Reactive oxygen species; Fluorenes derivatives; Human carcinoma cells; Nude mice model; Gold(I) complexes; Alkynes; Antineoplastic agent; Oxidative stress; Gold I Complexes; Acetylenic compound; Tertiary phosphine; Liver; Hepatocellular carcinoma; Cytotoxicity; Hepatocyte; Structure activity relation; Mammary gland; Chemical synthesis; Tumor cell; Univalent metal Complexes; Human; Rodentia; Organic ligand; Transition metal Complexes; Malignant tumor; Ketone; In vitro; Iron Organic compounds; In vivo; Vertebrata; Chemotherapy; Mu complex; Mammalia; Cell line; Treatment; Mouse; Animal; Dinuclear complex; Cancer
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2009.10.034

End-capping the diethynylfluorene unit with gold(I) moieties could significantly strengthen its cytotoxic activity on human cancer cells. Further study of the gold(I) derivative demonstrated its in vivo antitumor activity using Hep3B human hepatocellular carcinoma model with limited adverse effects on vital organs including liver and kidney.
A list of diethynylfluorenes and their gold(I) derivatives have been studied for their antitumor activity as a function of their structure–activity relationships. End-capping the fluoren-9-one unit with gold(I) moieties could significantly strengthen the cytotoxic activity in vitro on three human cancer cell lines with induction of reactive oxygen species generation on Hep3B hepatocellular carcinoma cells and exhibit attractive antitumor activity from in vivo nude mice Hep3B xenograft model with limited adverse effects on vital organs including liver and kidney.