Synthesis And Antitumor Activity Of Two Kinds Of Gold (?) Complexes

Following the major clinical successes achieved with platinum(?)complexes,toward a variety of cancers,the search for other metal compounds with improved therapeutic properties has been extremely active.Because of the use of cisplatin in cancer therapy is frequently associated with important drawbacks,including severe normal tissue toxicity and drug tolerance.In recent years,gold complexes as anticancer metal drugs have recently gained more attention due to its strong anti-proliferative ability.Many gold(?)compounds are practically ineffective in vivo,due to their potentiality of exchanging ligand with biomolecules,which usually leads to the reduction or even the loss of their activity.In this context,the alkyne gold(?)complex as bioactive reagents is considered to be an alternative to conventional gold(?)complexes.In order to find highly efficient lead structures,25 gold(?)complexes were designed and synthesized.The structure of the target compound was confirmed by NMR.MTT method was used to evaluate in vitro the activity of two kinds of gold(?)complexes.1?Firstly,MTT method was used to study the cytotoxicity of ten rigid dinuclear gold(?)complexes(2-1a~2-1j)against four tumor cells and two normal cells in vitro.The results indicated that all alkynyl(phosphine)gold(?)complexes functionalized with methoxy polyethylene glycols showed significant antitumor activity in vitro.In particular,complex 2-1j showed strong cytotoxicity and high selectivity to A549 cell lines.And the toxicity of complex 2-1j was much lower than that of standard drug cisplatin against normal cells.The results showed the alkynyl(phosphine)gold(?)complexes functionalized with methoxy polyethylene glycols was a very good lead structure,which has further research value.2?Then,four mononuclear alkynyl(triphenylphosphine)gold(?)complexes3-5a~3-5d and two flexible dinuclear alkynyl(triphenylphosphine)gold(?)complexes 3-9a~3-9b were successfully synthesized.The preliminary results showed that the mononuclear alkynyl(triphenylphosphine)gold(?)complexes functionalized with methoxy polyethylene glycols showed higher activity against Hela cells and HepG line cells,which was stronger than that of the mononuclear complexes functionalized without methoxy polyethylene glycols.Among them,the complex 3-5bfunctionalized with ethylene glycol monomethyl ether showed good activity against two cancer cells,and the toxicity against L6 cell lines was much less than that of cisplatin.However,two flexible dinuclear alkynyl(triphenylphosphine)gold(?)complexes 3-9a~3-9b showed moderate activity against two cancer cells.The preliminary results showed that the mononuclear gold complex functionalized with methoxy polyethylene glycols was a good lead structure,which has further research value.3?In addition,three heteronuclear iron(?)-alkynyl gold(?)complexes4-5a~4-5c were successfully obtained.The preliminary results showed that the activity of the complex 4-5c was good against two cancer cell lines,and the cytotoxicity against L6 cell lines was much less than that of cisplatin.4? At last,six heteronuclear iron(?)-gold(?)-dithiocarbamate complexes5-3a~5-3f were successfully synthesized.The preliminary results indicated the activity of the complex 5-3d substituted with piperidine was good against two cancer cell lines,and the cytotoxicity against L6 cell lines was much less than that of cisplatin.The structure needs to be further optimized.