Antitumoral Activity of Non-Platinum Xanthate Complexes

Abstract

To establish structure-activity relationships, derivatives of bis(O-alkyldithiocarbonato)platinum(II) complexes were analyzed. Eighteen bis(O-alkyldithiocarbonato) metal complexes were synthesized, and their cytotoxic activity on two human cancer cell lines was compared with the corresponding platinum bis(O-alkyldithiocarbonato) complexes and cisplatin. Complexes were synthesized with palladium, gold, nickel, copper, rhodium, and bismuth. Palladium and bismuth complexes were found to display significant cytotoxic activity. Palladium complexes were most active with up to 10-fold lower IC50 values as compared with the corresponding platinum complexes. The other complexes were only poorly active. Palladium, bismuth, and nickel complexes were more active at pH 6.8 than at pH 7.4. This difference in activity was most pronounced with palladium complexes. A pH of 6.8 and lower has been frequently found in solid tumors. Drugs with such pH dependent activity are supposed to have an improved therapeutic index as compared to drugs that are active irrespective of pH.

Cancer cell death induced by phosphine gold(I) compounds targeting thioredoxin reductase

“…In this field, other studies [55] indicated that xanthate complexes of several metals, including gold, palladium and bismuth, are endowed with a high antitumor activity. It has also to be considered that xanthate ligands are reported to be, in general, less toxic than dithiocarbamate ligands [11].…”

Anticancer Activity of Molecular Compounds of Arsenic, Antimony and Bismuth

“…By contrast, the R ¼ cyclohexyl derivative was significantly less cytotoxic against MCF 7 (mammary carcinoma), which is relatively non responsive to cisplatin (I), than the compounds with smaller R groups. Interestingly, when cytotoxicity was scored at pH ¼ 6.8, mimicking the pH of a solid tumour, the potency was greater for the R ¼ Et and i-Pr compounds [77]. It was determined that the comparable binary platinum(II) xanthates were significantly more cytotoxic than the bismuth compounds which have potency comparable to cisplatin (I).…”

Synthesis, crystal structures and cytotoxicities of some transition metal complexes with N-[2-{(pyridin-2-ylmethylidene)amino}ethyl]acetamide

“…The anticancer potential of the complexes was evaluated in two human cancer cell lines which were either highly sensitive (MOLT-4) [17] or poorly sensitive (MCF-7) [18][19][20] to cisplatin. For comparison purposes, the in vitro cytotoxicity of these compounds against Chang Liver cell line was also studied.…”

“…Results are expressed in terms of IC 50 values, i.e., the concentration of drug required to inhibit cell growth by 50%. Results are summarized in Table 4, together with the reference standard cisplatin [17,18].…”