Oehninger, L., Alborzinia, H., Ludewig, S., Baumann, K., Wölfl, S. and Ott, I. (2011), From Catalysts to Bioactive Organometallics: Do Grubbs Catalysts Trigger Biological Effects?. ChemMedChem. doi: 10.1002/cmdc.201100308
Organometallic compounds are primarily used in catalysis, however, some of them have been found to have important biological properties as well. In the early 60s’, the discovery that some platinum complexes had the ability to inhibit the division of living cells led to the development of several platinum-containing anti-cancer drugs such as cisplatin, carboplatin or oxaliplatin.
To date, platinum remains the major player in the development of new bioactive metal complexes, but ruthenium containing agents have also shown some promise. Two ruthenium[III] anticancer agents NAMI-A and KP1019 are currently in clinical trials. Half-sandwich ruthenium[II] complexes such as RM175 or RAPTA-C also exhibit interesting activities, which prompted researchers in Germany to investigate the possible biological relevance of other well-known ruthenium[II] complexes: the Grubbs-type catalysts G1, G2, HG1 and HG2.
All catalysts were found to inhibit tumor-relevant enzymes such as the thioredoxin reductase (TrxR) and the protease cathepsin B (catB). The inhibition of the enzymatic activity was observed with the order of activity G1<G2<HG1<HG2. For the second-generation Hoveyda-Grubbs complex HG2, the EC50 values were in the low micromolar range, values comparable to those reported for RAPTA-type complexes.
The ability of the catalysts to inhibit the growth of cultured tumor cells (MCF-7 breast adenocarcinoma and HT-29 colon carcinoma cells) was also probed. Once again, the second-generation Hoveyda-Grubbs was the most potent, and displayed noticeable antiproliferative effects with IC50 values of 9.9 µm (MCF-7) and 13.4 µm (HT-29). For reference, in the same assay, the IC50 values for cisplatin are 2.0 µm (MCF-7) and 7.0 µm (HT-29).
Finally, G1, G2 and HG2 were also found to influence cell metabolism.
Even though Grubbs catalysts are not potent enough to be the next anti-cancer drugs, they undeniably displayed a certain biological activity, especially for the second generation. Further investigation on the toxicity and specificity of Grubbs-type catalysts would be very useful.