Synthesis and antitumor activity of novel alkynyl (phosphine) digold(I) complexes

A series of 1,4-disubstituted digold–alkynyl complexes, [(PPh 3 )Au] 2 ( μ -C≡C – Ar–CH≡C)], in which the 1,4-diethenylbenzene bridge contains two alkyl or oligo(ethylene glycol)methylether side chains at different positions (2,5- and 2,3-positions), have been synthesized and structurally characterized by spectroscopic techniques. The structure of [(AuPPh 3 ) 2 {µ-C≡C–C 6 H 2 (OC 6 H 13 ) 2 -2,5-C≡C}] ( 2c ) has been established by X-ray crystallography. Their antitumor activities in vitro were investigated by MTT assay against four tumor cell lines. Compared to alkyl-functionalized complexes, the oligo(ethylene glycol)methylether-functionalized complexes showed significant antitumor activity, which may be attributed to the improvement of the hydrophilicity of the complex to achieve the appropriate lipophilicity. In particular, complex [(AuPPh 3 ) 2 {µ-C≡C–C 6 H 2 (OCH 2 CH 2 OCH 2 CH 2 OCH 3 ) 2 -2,3-C≡C}] ( 2j ) displayed high activity against the A549 cell line and low cytotoxicity toward normal cell lines. Notably, further investigations are required if complex 2j is to undergo trials as a new potential antitumor agent.