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Ten new vanadocene complexes bearing N , N ′-chelating ligands were prepared, characterized, and their cytotoxicity toward a panel of cancer cells was measured. Structures of four vanadocene compounds were determined by single crystal X-ray diffraction analysis. Complexes containing 1,2-bis(phenylimino)acenaphthene (bian) and 1,2-bis(4-methoxyphenylimino)acenaphthene (4-MeO-bian) exhibit higher cytotoxicity than those with dipyrido[3,2- a :2′,3′- c ]phenazine (dppz) and (E)- N -((pyridin-2-yl)methylene)benzenamine (pyma). In light of the finding, cytotoxic mechanisms of two highly effective complexes [(η5-C 5 H 4 Me) 2 V(bian)][OTf] 2 (3b) and [(η5-C 5 H 4 Me) 2 V(4-MeO-bian)][OTf] 2 (4b) against human A549 lung adenocarcinoma cells were investigated by following membrane leakage of intracellular lactate dehydrogenase, Trypan Blue staining and activation of tumor protein p53 (p53). Evaluated complexes have a potent dose-dependent antiproliferative activity, causing cell cycle redistribution by the increased accumulation of cells in the G2 and S phase. In accord with the observed cell cycle deceleration, cyclin-dependent kinase inhibitor-interacting protein 1 (p21WAF1/Cip1), extracellular signal–regulated kinases 1 and 2 (ERK1/2), Checkpoint kinase 1 (Chk1), Checkpoint kinase 2 (Chk2) and their phosphorylated forms Chk1 at serine 345 and Chk2 at threonine 68 increased. In the cells exposed to complexes, dose- and time-dependent apoptotic process is initiated by the activation of the initiator caspase 8, followed by activation of effector caspase 3/7 and phosphatidylserine externalization. Moreover, because of treatment, A549 cells activate prosurvival mitogen-activated protein kinases (MAPK) signaling and up-regulate antiapoptotic protein B-cell lymphoma (Bcl-2), thereby promoting evasion of cell death. Both complexes exhibited considerably higher cytotoxic effect than the reference anticancer drug cis -platin and the cytotoxicity was more pronounced at higher treatment time. The newly synthetized vanadocene complexes bearing N , N′ -ligands were tested on the cancer cell line. Experimental methods showed that the complexes of bis(phenylimino)acenaphthenes have higher cytotoxic effect than cis -platin but mechanism of the effect is similar to cis -platin. Unlabelled Image • Newly synthetized N , N′ -vanadocene complexes were tested for anti-cancer activity. • Their cytotoxic effect is higher than cis -platin. • Molecular action is based on the block cell cycle. • Tumor protein p53 (p53) and mitogen-activated protein kinases (MAPK) are activated. [ABSTRACT FROM AUTHOR]

Graphical abstract Series of vanadocene compounds bearing dithiocarbamate ligands was synthesized and characterized. The cytotoxicity study was performed on human leukemia cells MOLT-4 revealed strong cytotoxicity for species bearing cyclic dithiocarbamates. Highlights • Water-soluble vanadocene dithiocarbamate complexes were prepared. • Spectroscopic and X-ray crystallographic data are presented. • Cytotoxicity toward leukemia cells MOLT-4 was documented. Abstract This study describes synthesis of water-soluble vanadocene and 1,1′-dimethylvanadocene compounds bearing dithiocarbamate ligands. All prepared compounds were characterized by analytical and spectroscopic methods. The structure of [(η 5-C 5 H 4 Me) 2 V{S 2 CN(CH 2) 4 O}]Cl was determined by single-crystal X-ray diffraction analysis. The cytotoxicity of the synthesized compounds was investigated on human leukemia cells MOLT-4. The derivatives bearing cyclic dithiocarbamates show considerably stronger activity than reported for cisplatin. [ABSTRACT FROM AUTHOR]

This work describes a procedure giving cyclopentadienyl molybdenum(II) compounds bearing carboxylic acid function group. It involves synthesis of carboxylic acid ester functionalized cyclopentadienides, their coordination to molybdenum(II) precursor and saponification of ester function groups. The method is not limited only to compounds with the function group directly attached in the cyclopentadienyl ring but also to those functionalized in the side chain. The attempts to synthesize the indenyl analogues were only partially successful due to low stability in the saponification step. All reported structure types were elucidated from spectroscopic measurements and verified by X-ray crystallography. The second part of the work describes an effect of the outer-coordination sphere on cytotoxicity of the cationic molybdenum(II) compounds bearing N,N -chelating ligands. The cytotoxicity of the modified species bearing phenanthroline ligand toward human leukemia cells MOLT-4 (IC 50  = 10.5 ± 0.5 μmol l −1 ) is higher than reported for cisplatin (IC 50  = 15.8 ± 1.9 μmol l −1 ). [ABSTRACT FROM AUTHOR]