Potent Platinum(IV) Prodrugs That Incorporate a Biotin Moiety to Selectively Target Cancer Cells.

Four platinum(IV) prodrugs incorporating a biotin moiety to selectively target cancer cells were synthesised, characterised, and their biological activity assessed. All complexes exhibited exceptional in vitro cytotoxicity against a panel of cancer cell lines, with [Pt(5,6-dimethyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)(biotin)(hydroxido)](NO3)2, (2) exhibiting the lowest GI50 of 4 nM in the prostate Du145 cancer cell line. Each complex displayed significantly enhanced activity compared to cisplatin, with 2 being 1000-fold more active in the HT29 colon cancer cell line. Against the MCF-7 breast cancer cell line, in which high levels of biotin receptors are expressed, 2, [Pt(4,7-dimethoxy-1,10-phenanthroline)(1S,2S-diaminocyclohexane)(biotin)(hydroxido)](NO3)2, (3), and [Pt(5-methyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)(biotin)(hydroxido)](NO3)2, (4) exhibited enhanced activity compared to their platinum(II) cores, with 4 being 6-fold more active than its platinum(II) precursor. Furthermore, 3 exhibited 3-fold greater selectivity towards MCF-7 breast cancer cells compared to MCF10A breast healthy cells, and this was further confirmed by platinum uptake studies, which showed 3 to have almost 3-fold greater uptake in MCF-7 cells, compared to MCF10A cells. The results show that lipophilicity and selectivity both contributed to the cellular uptake of 1-4; however, this was not always translated to the observed cytotoxicity.

Coal tailings as a soil conditioner: evaluation of tailing properties and effect on tomato plants.

The global coal industry yields a vast amount of tailings waste, and the utilisation of these tailings necessitates innovative efforts contributing to the United Nations Sustainable Development Goals. One of such novel initiatives is to reuse coal tailings (CT) safely, ecofriendly, and cost-effectively in agroecosystems as a soil conditioner to enhance the productivity of lands. This study aimed to evaluate the potential utilisation of coal tailings waste in the soil amelioration to improve plant performance. The physico-chemical characteristics of coal tailings from two Australian mining sites (CT1 and CT2) showed that the tailings samples are alkaline with loamy and loamy sand textures, respectively. The tailings have ~ 3% of macronutrients, high carbon (C), and low heavy metals and metalloids (As, Cd, Se, Cu, Zn, and Pb). The germination rate of tomato seeds was improved in the low-rate CT treatment. Greenhouse tomato plants exhibited an increase in leaf's K, Ca, and Mg contents in CT1 and CT2 treatments. More importantly, the CT treatment-induced accumulation of heavy metals in plants was mostly insignificant in both CT treatments. Therefore, we highlight the potential application of coal tailings as a soil conditioner because of the beneficial effect of improved carbon and nutrients (N, P, K, Mg, and Ca) in tomato leaves. Further amendment of the coal tailings should focus on the adjustment of pH and the addition of other beneficial materials for the improvement of soil properties for crops in both the greenhouse and the field.

Cyclooxygenase-Inhibiting Platinum(IV) Prodrugs with Potent Anticancer Activity.

Platinum(IV) prodrugs of the [Pt(PL)(AL)(COXi)(OH)]2+ type scaffold (where PL is 1,10-phenanthroline or 5,6-dimethyl-1,10-phenanthroline, AL is 1S,2S-diaminocyclohexane, and COXi is a COX inhibitor, either indomethacin or aspirin) were synthesised and characterised, and their biological activity was explored. MTT assays showed that these complexes exhibit outstanding activity against a range of cancer cell lines, and nanomolar activities were observed. The most potent complex, 4, exhibited a GI50 of 3 nM in the Du145 prostate cancer cell line and was observed to display a 1614-fold increased activity against the HT29 colon cancer cell line relative to cisplatin. ICP-MS studies showed a linear correlation between increased cellular accumulation of the complexes and increased cytotoxicity, while an enzyme immunoassay showed that 1 and 2 inhibited COX-2 at 14 and 1.4 µM, respectively, which is comparable to the inhibition exhibited by indomethacin. These results suggest that while the cytotoxicity of prodrugs 1-4 was influenced by cellular uptake, it was not entirely dependent on either COX inhibition or lipophilicity.