Other medicinal applications

Anti-cancer activities of antimony agents have also been reported. Antimony tartrate has been found to be cytotoxic in vitro to various lung cancer cell lines with IC50 ranging from 4.2 to 322 mgml"1. The complex was found to be as effective as those clinically used anti-cancer drugs such as cisplatin and doxo-rubicin.30 Other antimony compounds (including organometallic complexes) have been tested in both cell cultures and animal models, and have displayed moderate activities.31

The anti-cancer activity of sodium stibogluconate that synergizes with interferon-« (IFN-a) to eradicate IFN-a-resistant human cancer cells both in vitro and in mouse models has been reported.32 It was shown that the complex functions as a protein tyrosine phosphatase (PTPase) inhibitor in cancer cells and augments IFN-a signaling.33 The activity of Src homology PTPase1 (SPH-1) was almost completely inhibited by sodium stibogluconate at 10 mgml"1, which is comparable to the serum concentration of Leishmania treatment (^10 mgml"1). The inhibition is likely to target the catalytic domain of PTPase. Interference with the intracellular tyrosine phosphorylation resulted in the disruption of the cell proliferation, differentiation and signaling activities, with

consequent anti-tumor activity.

Since sodium stibogluconate is a polymeric complex, the inhibitory activities of different fractions from HPLC toward PTPase have been determined. It has become evident that a small portion of the fractions in sodium stibogluconate is mainly responsible for the PTPase inhibitory activity and that interestingly it is not solely defined by antimony contents. It might be feasible to develop more specific and effective inhibitors for phosphatase-targeted anti-cancer therapeutics through the screening of sodium stibogluconate-related compounds, comprised of antimony conjugated to different organic moieties. Sodium stibogluconate appears to be a better inhibitor than suramin, a compound known for its anti-neoplastic activity against several types of cancers,35 38 and new therapeutic applications of sodium stibogluconate targeting the phos-phatase have then been explored.

Hepatitis C virus (HCV) is a blood-borne virus, previously the most common causative agent of post-transfusion non-A and non-B hepatitis. Recently, it has been reported that sodium stibogluconate is effective in suppressing HCV replication in a HCV-permissive cell line as well as in fresh human liver slices obtained from HCV-infected patients.39 The anti-viral effect of the drug was subsequently verified using a cell line (293EBNA-Sip-L) and was proved to be permissive for HCV infection/replication. A nearly complete suppression effect was achieved in four out of six human liver slices at the concentration of 100 mg/ml, lower than that required for the treatment of leishmaniasis (recommended dose: 20 mg kg"1 day"1).

In the mid-1980s, antimoniotungstate ([(NH4)17Na(NaSb9W21O86)-14H2O], HPA-23) was reported to be active in reducing HIV levels in a patient with AIDS.40 This observation stimulated the search for other polyoxometalates as potential anti-HIV agents. The median effective concentration (EC50) and inhibitory concentration (IC50) values of HPA-23 are 0.39 and 35 mM, respectively in human peripheral blood mononuclear (PBM) cells for its anti-HIV

activity and toxicity.41 Other polyoxometalates were also found to be active in this cell line. A structural study of HPA-23 showed that it has C3h molecular symmetry with six possible sites where additional metal ions could bind.42,43

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