Development of cobalt(3,4-diarylsalen) complexes as tumor therapeutics.
[1,6-Bis(2-hydroxyphenyl)-3,4-diaryl-2,5-diazahexa-1,5-diene]cobalt(II) complexes (cobalt(3,4-diarylsalen)) with 2-, 3-, or 4-OCH(3)/OH substituents in the 3,4-standing aryl rings were synthesized and tested for antitumor activity in vitro on the MCF-7, MDA-MB 231, and LNCaP/FGC cell lines. The cytotoxicity depended on both the configuration of the diene ligand and the kind of substituents in the 3,4-standing aromatic rings. d,l-7 (2-OCH(3)), d,l-8 (3-OCH(3)), and d,l-9 (4-OCH(3)) were equipotent to cisplatin, while the respective hydroxy-substituted complexes (d,l-10 (2-OH), d,l-11 (3-OH), and d,l-12 (2-OH)) as well as all of the meso-configured compounds (m-7 to m-12) did not influence the cell growth. Interestingly, a high catalytic potency and a rapid and high accumulation in MCF-7 cells (15- to 25-fold compared to the cell culture medium (5 microM)) were demonstrated for m-7 (2-OCH(3)), m-8 (3-OCH(3)), and m-9 (4-OCH(3)). Therefore, a mode of action based on a cobalt-catalyzed oxidative damage of the DNA is not very likely.
Gust
Ronald
R
Institute of Pharmacy, Free University of Berlin, Königin-Luise Strasse 2+4, D-14195 Berlin, Germany. rgust@zedat.fu-berlin.de
Ott
Ingo
I
Posselt
Diana
D
Sommer
Klaus
K
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002384:Catalysis; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry; D003035:Cobalt; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001372:Aza Compounds; D002614:Chelating Agents; D009942:Organometallic Compounds; D003035:Cobalt