title: Synthesis and structure-activity relationship of novel antitumoral platinum xanthate complexes.
abstract: To establish structure-activity relationships, derivatives of a recently described sulfur-containing antitumoral platinum complex, bis(O-ethyldithiocarbonato)platinum(II), named thioplatin, were analyzed. Twenty different bis(O-alkyldithiocarbonato)platinum(II) complexes were synthesized and tested for cytotoxic activity in a panel of six human tumor lines. Derivatives with up to 7-fold increased activity compared to thioplatin and up to 25-fold more activity than cisplatin were identified. Bis(O-alkyldithiocarbonato)platinum(II) complexes with short n-alkyl chains such as methyl, ethyl, propyl, and butyl were found to be superior to compounds with long n-alkyl chains such as hexyl, octyl, and decyl. Complexes derived from secondary xanthates displayed significantly higher activity than those derived from primary xanthates with the same number of C atoms. Like thioplatin, all tested platinum complexes were more active at pH 6.8 than at pH 7.4. A pH of 6.8 and lower has been frequently found in solid tumors because of the tendency of tumor cells to undergo anaerobic fermentation. Drugs with such pH-dependent antitumoral activity have an improved therapeutic index compared to drugs that are active irrespective of pH.
authors.affiliation: Department D060, German Cancer Research Centre, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Friebolin
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schilling
authors.forename: Margot
authors.initials: M
authors.lastname: Zöller
authors.forename: Eberhard
authors.initials: E
authors.lastname: Amtmann
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013457:Sulfur Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D013457:Sulfur Compounds; C431426:thioplatin