Synthesis, characterization, and in vivo evaluation of the anticancer activity of a series of 5- and 6-(halomethyl)-2,2'-bipyridine rhenium tricarbonyl complexes.

We report the synthesis, characterization, and in vivo evaluation of the anticancer activity of a series of 5- and 6-(halomethyl)-2,2'-bipyridine rhenium tricarbonyl complexes. The study was promoted in order to understand if the presence and position of a reactive halomethyl substituent on the diimine ligand system of fac-[Re(CO)3]+ species may be a key molecular feature for the design of active and non-toxic anticancer agents. Only compounds potentially able of ligand-based alkylating reactions show significant antiproliferative activity against colorectal and pancreatic cell lines. The anticancer potency of the species, does not correlate with the hydrolysis rate or rate of reaction of the coordinated 5- and 6-(halomethyl)-2,2'-bipyridine with the amino acid lysine. Of the new species presented in this study, one compound (5-(chloromethyl)-2,2'-bipyridine derivative) shows significant inhibition of pancreatic tumour growth in vivo in zebrafish-Panc-1 xenografts. The complex is noticeably effective at 8 uM concentration, lower than its in vitro IC50 values, being also capable of inhibiting in vivo cancer cells dissemination.