Alkyne hexacarbonyl dicobalt complexes in medicinal chemistry and drug development

Abstract

Background : Organometallic alkyne complexes of the hexacarbonyl dicobalt type (hexacarbonyl[ µ -h 4 -(alkyne)]dicobalt (Co -Co) complexes) are an interesting class of compounds used in modern synthetic chemistry and an increasing number of reports deal also with the use of these complexes in the field of medicinal chemistry. Methods : This review highlights the applications of alkyne hexacarbonyl dicobalt species in biomedical research with a focus on anticancer drug development. Medline, Pubmed, Scifinder and Espacenet internet databases were searched for available literature and patents. Results/conclusion : Preclinical studies on hexacarbonyl dicobalt complexes containing various alkyne (bio)ligands demonstrated a high potential for application (e.g., as antitumor drugs, hormonally active or diagnostic agents). The biological properties of the compounds were mainly determined by the nature of the ligands and the presence of the metal center.

Extremely Tight Binding of a Ruthenium Complex to Glycogen Synthase Kinase 3

“…Such a dramatic effect by replacing a CO ligand with a cyanide we have observed before in a related octahedral scaffold. [19] Although isoelectronic, coordinated CO is hydrophobic, [20,21] whereas coordinated cyanide tends to form hydrogen bonds with its nitrogen lone pair and will therefore not have any desire to bind into the hydrophobic pocket build by the glycine-rich loop. [22,23] These examples demonstrate the importance of the CO group and, in fact, we have yet to find a highly potent and selective ruthenium complex for GSK-3 that lacks this apparently crucial CO ligand.…”

The synthesis and characterization of a series of cobalt(II) β-ketoaminato complexes and their cytotoxic activity towards human tumor cell lines

“…6), is a common mechanism of action for many anti-cancer drugs [42] including cisplatin [43]. As well, the PC-3 cell death caused by three of the most active cobalt compounds (L 1 Co, L 2 Co, and L 3 Co) appears dependent on activation of MAP kinases, and JNK in particular, a mechanism that has also been widely implicated in apoptosis as induced by cisplatin and other anti-cancer drugs [12,44].…”

“…Ott et al have reported the synthesis and antitumor efficacy of [2-acetoxy-(2-propynyl)benzoate] hexacarbonyldicobalt [11]. Its mode of activity against cancer cells is unknown but it has been suggested that these complexes may interact with DNA or DNA-related cellular biochemical pathways [12]. A number of cobalt(III) complexes have been examined for their antiviral properties, with the most significant development being the approval of Doxovir as a topical microbicide for the treatment of herpes simplex virus type 1 [13].…”

Anticancer (hexacarbonyldicobalt)propargyl aryl ethers: Synthesis, antiproliferative activity, apoptosis induction, and effect on cellular oxidative stress

“…Among its many other demonstrated biological effects was a strong induction of caspase-3, which is an important activator in apoptosis. Several other anticancer (hexacarbonyldicobalt)alkyne compounds have also been reported [16]; in all cases, the bioactivities of these compounds have been shown to depend on both the hexacarbonyldicobalt moiety and the organic ligand.…”