Synthesis, toxicities and bio-activities of manganese complexes with CO and H 2 S dual donors.

A series of H2 SCO dual-donors [Mn(CO)4 CS2 NR1 R2 ] was synthesized, and evaluated from toxicity and bioactivity. The COH2 S measuring test showed all the complexes not only released CO, but released H2 S. The resulting data of cytotoxicity showed all the complexes had activities against the cell proliferation; among them, complexes 1, 2 and 7 displayed higher activities than the others, and their potencies were close to cis-platinum (DDP); whereas the precursors A1 -A22 had almost no activities against all five tumor cell lines and W138 cell line proliferation. It is worth noting that complex 1 displayed the highest activity to MCF-7, complex 2 displayed the highest activity to HePG2, and complex 7 showed selectivity inhibition to both A549 and HeLa. The developmental toxicities of the complex were assessed using zebrafish embryos. The results showed complexes 1 and 2 had effect on the mortality and hatching rate of zebrafish embryos in dose-dependent manner. They caused zebrafish malformations when they were over 10 μM. Meanwhile, they displayed dose-dependent toxicities to larval zebrafish. In the test of bio-activities, complexes 1 and 2 had strong anti-inflammatory activities; they not only down-regulated the expression levels of iNOS and TNF-α, up-regulated the expression of HO-1 and IL-10, but also up-regulated COX-2 levels. In contrast, the precursor compound (A1 or A2 ) displayed lower anti-inflammatory activity than the corresponding complex, which suggests both the CO and H2 S from the complex took synergistic effects in the process of anti-inflammation. In addition, the complex showed antihypertensive effect and myocardial protection. This effect also possibly resulted from this synergistic effect. All these suggest the complexes have potential to be candidate medicines.