24640-95-7Relevant academic research and scientific papers
Discovery and investigation of anticancer ruthenium-arene Schiff-base complexes via water-promoted combinatorial three-component assembly
Chow, Mun Juinn,Licona, Cynthia,Yuan Qiang Wong, Daniel,Pastorin, Giorgia,Gaiddon, Christian,Ang, Wee Han
, p. 6043 - 6059 (2014)
The structural diversity of metal scaffolds makes them a viable alternative to traditional organic scaffolds for drug design. Combinatorial chemistry and multicomponent reactions, coupled with high-throughput screening, are useful techniques in drug discovery, but they are rarely used in metal-based drug design. We report the optimization and validation of a new combinatorial, metal-based, three-component assembly reaction for the synthesis of a library of 442 Ru-arene Schiff-base (RAS) complexes. These RAS complexes were synthesized in a one-pot, on-a-plate format using commercially available starting materials under aqueous conditions. The library was screened for their anticancer activity, and several cytotoxic lead compounds were identified. In particular, [(η6-1,3,5-triisopropylbenzene)RuCl(4-methoxy-N-(2- quinolinylmethylene)aniline)]Cl (4) displayed low micromolar IC50 values in ovarian cancers (A2780, A2780cisR), breast cancer (MCF7), and colorectal cancer (HCT116, SW480). The absence of p53 activation or changes in IC50 value between p53+/+ and p53-/- cells suggests that 4 and possibly the other lead compounds may act independently of the p53 tumor suppressor gene frequently mutated in cancer.
Structural determinants of p53-independence in anticancer ruthenium-arene Schiff-base complexes
Chow, Mun Juinn,Babak, Maria V.,Wong, Daniel Yuan Qiang,Pastorin, Giorgia,Gaiddon, Christian,Ang, Wee Han
, p. 2543 - 2554 (2016)
p53 is a key tumor suppressor gene involved in key cellular processes and implicated in cancer therapy. However, it is inactivated in more than 50% of all cancers due to mutation or overexpression of its negative regulators. This leads to drug resistance
