We have recently shown a range of organometallic complexes with significant potential as anticancer drugs. A major problem of drug formulation is the presence of isomers in solution, and the straightforward design of isomerically pure drugs. This work will present new ways to combat these issues with complexes of the type [MX2L2]. A library of bis-picolinamide metal dihalide complexes of the type [MX2L2] (M = Ru/Rh, X = Cl/I and L = picolinamide) has been synthesised and structural studies revealed a mixture of cis and trans isomers for the [MCl2L2] complexes. Changing the halide to iodide, [MI2L2], generates exclusively a single trans isomer. We present the synthesis of trans metal compounds with high anti-cancer potencies in the nanomolar range against various cancer cell lines. The chemosensitivity studies will be presented, with potencies for selected complexes similar to or better than cisplatin. The data against healthy cells, results under hypoxic conditions and hydrolysis studies will also be presented. The results will be further discussed in contrast to earlier literature which considered many trans complexes to be inactive due to high kinetic instability. In conclusion, the change in configuration to a stable trans isomer triggers high in vitro activity as well as high cancer cell selectivity and the complexes remain active under hypoxic conditions. These findings highlight these new complexes as excellent drug candidates for further in vivo studies.

Bis-picolinamide metal dihalide complexes: Trans isomers with significantly high potency and cancer cell selectivity

254th National Meeting (2017)

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