RESUMO
The availability of metamizole varies greatly around the world. There are countries such as the USA, UK, or Australia where the use of metamizole is completely forbidden, and there are also countries where this drug is available only on prescription (e.g., Greece, Italy, Spain, etc.) and those in which it is sold OTC-over the counter (e.g., most Asian and South American countries). Metamizole, as a drug with a strong analgesic effect, is used as an alternative to other non-steroidal anti-inflammatory drugs, alone or in combination with opioid drugs. Risedronate sodium is a third-generation bisphosphonate commonly used in orthopaedic and metabolic diseases of the musculoskeletal system, including hypercalcemia, postmenopausal osteoporosis, Paget's disease, etc. The aim of this study was to check whether there were any pharmacological interactions between metamizole and risedronate sodium in in vitro studies. Cell viability was assessed using the MTT method, the number of apoptotic cells was assessed using the labelling TUNEL method, and the cell cycle assessment was performed with a flow cytometer and propidium iodide. This was a pilot study, which is why only two cancer cell lines were tested: D-17 of canine osteosarcoma and U-2 OS of human osteosarcoma. Exposure of the canine osteosarcoma cell line to a combination of risedronate sodium (100 µg/mL) and metamizole (50, 5, and 0.5 µg/mL) resulted in the complete abolition of the cytoprotective activity of metamizole. In the human osteosarcoma cell line, the cytotoxic effect of risedronate sodium was entirely eliminated in the presence of 50 µg/mL of metamizole. The cytoprotective and anti-apoptotic effect of metamizole in combination with risedronate sodium in the tested human and canine osteosarcoma cell lines indicates an urgent need for further in vivo studies to confirm or disprove the potential dose-dependent undesirable effect of such a therapy.
RESUMO
This study presents a simple and energy-efficient self-assembly LAG synthetic method for novel water-soluble copper(I) complexes [Cu(terpy)(PTA)][PF6] (1) and [Cu(terpy)(PTA)2][PF6] (2). They were characterized by FT-IR, 1H, and 31P{1H} NMR spectroscopy, elemental analysis, and single-crystal/powder X-ray diffraction (for 2). The X-ray analysis of compound 2 indicates a bidentate coordination mode of terpyridine to the metal center. Variable-temperature NMR tests indicate dynamic properties for terpyridine in the case of both compounds, as well as for the PTA ligands in the case of 2. Additionally, compounds 1 and 2 exhibit interesting cytotoxic activity, which was tested on normal human dermal fibroblasts (NHDFs), human lung carcinoma (A549), human breast adenocarcinoma (MCF-7), and human cervix carcinoma (HeLa) established cell lines. In comparison to the other tested compounds, complexes 1 and 2 seem to have significantly lower IC50 values against cancer cells (A549, HeLa, MCF-7), indicating their potential as prospective anticancer agents. Moreover, both compounds show no significant toxicity towards normal skin cells (NHDFs), suggesting a certain selectivity in their action on cancer cells. Cisplatin as a reference compound also exhibited considerable cytotoxicity against cancer cells but with a low level of selectivity, which could lead to unwanted effects on normal cells. Remarkably, compounds 1 and 2 exhibit up to 30 times the cytotoxic activity of cisplatin, with a six-fold lower toxicity to normal cells. They also interact strongly with human serum albumin, suggesting potential therapeutic applications. Overall, these compounds hold significant promise as potential chemotherapeutic agents.
