One of the most widely used strategies for drug development is the coordination of bioactive ligands to transition metals, which could improve biological activity. Moreover, the incorporation of aromatic groups to ligands may allow an enhanced lipophilicity that can influence the cellular uptake and accumulation of the metallodrugs, thus increasing their activity. Herein, we have reported the synthesis and characterization of four Pt(II) complexes [PtCl₂(L)], where L = 2-(1-pyrazolyl)-2-thiazoline (PzTn), 2-(1-pyrazolyl)-1,3-thiazine (PzTz), 2-(3,5-diphenyl-1-pyrazolyl)-2-thiazoline (DPhPzTn) or 2-(3,5-diphenyl-1-pyrazolyl)-1,3-thiazine (DPhPzTz). The study was aimed at analysing their potential anticarcinogenic ability in epithelial cervix carcinoma HeLa, human promyelocytic leukemia HL-60 and human histiocytic lymphoma U-937 tumour cell lines as well as checking whether the structural factors of the organic ligand may influence their biological activity. Our findings showed that PtDPhPzTn and PtDPhPzTz were far more effective in terms of cytotoxicity than their less lipophilic counterparts (PtPzTn and PtPzTz), especially in cells derived from solid cervical tumours, thereby suggesting that modulating the lipophilicity of the ligands can help improve the cytotoxic effect of the metal complexes.

Chemical, pharmacological, and clinical research on anticancer coordination complexes has led to noteworthy anticancer drugs such as cisplatin, carboplatin and oxaliplatin. Although these compounds are effective chemotherapeutic agents in the treatment of different tumors, they are associated with high toxicity and numerous side effects. Several studies have shown that the range of platinum complexes with antitumor activity is not limited to structural analogs of cisplatin. Therefore, the development of convenient anticancer drugs that can be effectively used for the treatment of human tumors has become the main goal of most research groups in this field. In this sense, active platinum complexes without NH groups, transplatinum complexes, multinuclear complexes, cationic complexes, and several classes of palladium(II) complexes have emerged. Herein, the synthesis and characterization of two Pt(II) or Pd(II) complexes with PyTz (2-(2-pyridyl)iminotetrahydro-1,3-thiazine), a thiazine derivative ligand, with the formula [MCl₂(PyTz)]·C₂H₆O (M = Pt(II) or Pd(II)) were reported. The potential anticancer ability of both complexes was evaluated in epithelial cervix carcinoma HeLa, human ovary adenocarcinoma SK-OV-3, human histiocytic lymphoma U-937, and human promyelocytic leukemia HL-60 cell lines. Interestingly, the Pt(II) complex showed great cytotoxic potential against all tumor cell lines tested, whereas the Pd(II) complex displayed slight antitumor actions.

The synthesis of analogs of cisplatin, which is a widely used chemotherapeutic agent, using other metal centers could be an alternative for cancer treatment. Pd(II) could be a substitute for Pt(II) due to its coordination chemistry similarity. For that reason, six squared-planar Pd(II) complexes with thiazine and thiazoline ligands and formula [PdCl₂(L)] were synthesized and characterized in this work. The potential anticarcinogenic ability of the compounds was studied via cytotoxicity assay in three different human tumor cell lines, i.e., epithelial cervix carcinoma (HeLa), promyelocytic leukemia (HL-60), and histiocytic lymphoma (U-937). Data obtained showed that complexes with methyl substitutions did not modify cell viability, while no-methyl substituted compounds had a moderate cytotoxic effect on all three cell lines. The complexes with phenyl substitutions displayed the lowest IC₅₀ values, which ranged between 46.39 ± 3.99 μM and 62.74 ± 6.45 μM. Moreover, Pd accumulation inside the cell was observed after incubation with any of the four complexes mentioned, and the two complexes with phenyl rings were found to induce an increase in the percentage of apoptotic cells. These results suggested that the presence of bulky substitutions on the ligands such as phenyl groups may influence the cytotoxicity of the chemotherapeutic agents synthesized.