New complexes of platinum (II) and palladium (II) with derivatives of furan-2-carbaldehyde thiosemicarbazone and their antitumor activity

Cancer disease, characterized by the uncontrolled growth of abnormal cells, generates various neoplasms in different organs of the body. Due to the high mortality rate, cancer is considered one of the public health problems with the highest incidence in Peru, managing to identify different types of cancer in women (cervix and breast) and in men (stomach, lung and prostate). Cisplatin, Pt (NH3) 2Cl2, is the anticancer agent for clinical use, used in cancer chemotherapy. However, it has been shown that the compound 3-amino-pryridine-2-carbaldehyde thiosemicarbazone, inhibits the growth of human tumor cells: L1210 leukemia and A2780 ovarian carcinoma.
Continuing with the search for new compounds with potential antitumor activity, this work describes the preparation, characterization and cytotoxic evaluation in vitro of new complexes of platinum (II) with ligands derived from furan-2-carbaldehyde thiosemicarbazone against different cell lines human tumor.

Cisplatin [cis-Pt (NH3) 2Cl2] is the chemotherapeutic agent for clinical use that is used in the treatment of cancer and uses a concentration of 1 mg / mL intravenously in patients suffering from this disease. However, cisplatin produces side effects such as nausea, vomiting, diarrhea, stomach irritation, nephrotoxicity, and neurotoxicity. For this reason, the search for new very effective anticancer agents in some type of cancer and low toxicity is of great interest. Having evidence that some transition metal complexes with ligands derived from heterocyclic thiosemicarbazones have anticancer activity, our research group wishes to synthesize new complexes of platinum (II) and palladium (II) with ligands derived from X-furaldehyde-2- carbaldehyde thiosemicarbazone (X = Br, NO2, CH3, CF3, Ph, CH2OH, FPh, piperidinyl, naphthyl, pyrazoyl) and evaluate its cytotoxic activity

Graur et al. (2014) reported on the preparation of the ligand 5-nitrofuran-2-carbaldehyde-N (4) -allyl-3-thiosemicarbazone (HL) and its copper (II) complex, Cu (HL) 2 (NO3) 2, and in vitro cytotoxic evaluation against the human leukemia cell line (HL-60). The results indicated that the copper (II) complex (66% inhibition of cell growth) is more active than the coordination free ligand (57.7% inhibition of cell growth) at the concentration of 10-5 M. However, both the HL ligand and its copper (II) complex were not active at low molar concentrations of 10-6 and 10-7 M. The coordination of the ligand to the metal ion (Cu2 +) is an important factor for the increase in cytotoxicity . Probably, the moderate activity presented by the HL ligand would be related to the formation of the hydrogen bond between the oxygen of the furaldehyde and the cellular DNA (Akhtar et al., 2017).
In research projects carried out in previous years, Hernández et al., Showed that some heterocyclic derivatives of the thiazole-2-carbaldehyde thiosemicarbazone type show acceptable cytotoxic activity in vitro against different human tumor cell lines. The cytotoxic data obtained showed that some heterocyclic compounds derived from thiazothiosemicarbazone (IC50 = 7.14-13.68 µM) were very active against HUTU 80 (colon carcinoma) and MCF-7 (breast adenocarcinoma) cell lines. However, these thiosemicarbazone derivatives were 2-5 times less cytotoxic with respect to the antiproliferative activity of the clinically used antineoplastic drug, 5-fluorouracil.