Martina Řezáčová

Aim: This investigation was designed to synthesize half-sandwich Rh(III) and Ru(II) complexes and study their antiproliferative activity in human cancer cell lines. Materials & methods: Nine compounds were prepared and tested by various assays for their anticancer activity and mechanism of action. Results: Hit Rh(III) complex 6 showed low-micromolar potency in cisplatin-sensitive (A2780) and -resistant (A2780cis) ovarian carcinoma cell lines, promising selectivity toward these cancer cells over normal lung fibroblasts and an unprecedented mechanism of action in the treated cells. DNA synthesis was decreased and CDKN1A expression was upregulated, but p21 expression was not induced. Conclusion: Rh complex 6 showed high antiproliferative activity, which is induced through a p21-independent mechanism of action.

A series of molybdenum(II) compounds [(η 5 ‐Cp’)Mo(CO) 2 (L 2 )][BF 4 ] (Cp’=C 5 H 4 (CH 2 ) 2 SPh, C 9 H 6 (CH 2 ) 2 OMe, L 2= N,N ‐chelating ligand) have been synthesized and characterized by spectroscopic and analytical methods including X‐ray crystallography. The in vitro assay on human leukemia cells MOLT‐4 has shown that the substitution in the π‐ligand in combination with suitable N,N ‐chelating ligand can lead to species with cytotoxicity considerably higher than reported to cisplatin. Unusually high activity was observed for compounds bearing phenanthroline ligands [{η 5 ‐C 9 H 6 (CH 2 ) 2 OMe}Mo(CO) 2 (3,4,7,8‐Me 4 phen)][BF 4 ] (IC 50 =0.7±0.3 μM) and [{η 5 ‐C 9 H 6 (CH 2 ) 2 OMe}Mo(CO) 2 (4,7‐Ph 2 phen)][BF 4 ] (IC 50 values 0.8±0.4 μM).