The anticancer activity of platinum complexes has been known since the discovery of classical Pt(II)‐based drug cisplatin. However, Pt(IV) complexes have greater inertness than corresponding Pt(II) complexes, thus allowing the oral administration and reducing the toxicity associated with platinum‐based chemotherapy. Here, we describe the in vitro antitumor activity of some novel Pt(IV)‐based agents against mouse fibrosarcoma L929 cells and human astrocytoma U251 cells. The cytotoxicity of 2 Pt(IV) complexes with bidentate ethylenediamine‐N,N′‐di‐3‐propanoato esters was found to be markedly higher than that of their Pt(II) counterparts and comparable to the antitumor action of cisplatin. In contrast to cisplatin, which caused oxidative stress‐independent apoptotic cell death of tumor cells, these Pt(IV) complexes induced oxygen radical‐mediated tumor cell necrosis. Importantly, the cytotoxic action of novel Pt(IV) complexes was markedly more rapid than that of cisplatin, indicating their potential usefulness in anticancer therapy. © 2005 Wiley‐Liss, Inc.

The present study describes the ability of an anthraquinone derivative aloe emodin (AE) to reduce the cytotoxic activity of the platinum(II)-based anticancer agent cisplatin toward murine L929 fibrosarcoma and C6 glioma cell lines. The protective effect of AE was demonstrated by MTT and crystal violet assays for cell viability, and involved supression of cisplatin-induced apoptosis and necrosis, as assessed by lactate dehydrogenase release and flow cytometric analysis of DNA fragmentation or phosphatidylserine exposure. Cell-based ELISA and Western blot analysis revealed that AE abolished cisplatin-triggered activation of extracellular signal-regulated kinase (ERK) in tumor cells, while activation of c-Jun N-terminal kinase was not significantly altered. A selective blockade of ERK activation with PD98059 mimicked the protective effect of AE treatment in both tumor cell lines. Moreover, AE failed to protect tumor cells against the ERK-independent toxicity of the Pt(IV)-based complex tetrachloro(O,O-dibutyl-ethylenediamine-N,N'-di-3-propanoate)platinum(IV). Taken together, these data indicate that herbal anthraquinone AE can downregulate the anticancer activity of cisplatin by blocking the activation of ERK in tumor cells.

Anew bidentate ligand butyl-(1-methyl-3-phenyl-propyl)-dithiocarbamate (bm?pdtc) was prepared, as the sodium salt. In the reaction of hexaaminecobalt(III) chloride with Nabm?pdtc, the corresponding tris[butyl-(1-methyl-3-phenyl-propyl)-dithiocarbamato]cobalt(III) [Co(bm?pdtc)3]?complex was prepared. The complex was characterized by elemental analysis, infrared, electronic absorption, 1H and 13C-NMR spectroscopy.

Two new p-cymene ruthenium(II) complexes containing as additional ligands N-methylpiperazine ([(η 6 -p-cymene)RuCl 2 (CH 3 NH(CH 2 ) 4 NH)]PF 6 , complex 1) or vitamin K 3 -thiosemicarbazone ([(η 6 -p-cymene)RuCl 2 (K 3 tsc)], complex 2) were synthesized starting from [(η 6 -p-cymene) 2 RuCl 2 ] 2 and the corresponding ligand. The complexes were characterized by elemental analysis, IR, electronic absorption and NMR spectroscopy. The X-ray crystal structure determination of complex 1 revealed "piano-stool" geometry. The differences in the cytotoxic activity of the two complexes are discussed in terms of the ligand present.