Ivan Potočňák

Derivatives combining acridine, pyrrole, and thiazolidine rings have emerged as promising candidates in the field of antitumor drug discovery. This paper aims to highlight the importance of these three structural motifs in developing potent and selective anticancer agents. The integration of these rings within a single molecule offers the potential for synergistic effects, targeting multiple pathways involved in tumor growth and progression. Spiro derivatives were efficiently synthesized in a two-step process starting from isothiocyanates and 2-cyanoacetohydrazide. The thiourea side chain in spiro derivatives was utilized as a key component for the construction of the thiazolidine-4-one ring through regioselective reactions with bifunctional reagents, namely methyl-bromoacetate, dietyl-acetylenedicarboxylate, ethyl-2-bromopropionate, and ethyl-2-bromovalerate. These reactions resulted in the formation of a single regioisomeric product for each derivative. Advanced spectroscopic techniques, including 1D and 2D NMR, FT-IR, HRMS, and single-crystal analysis, were employed to meticulously characterize the chemical structures of the synthesized derivatives. Furthermore, the influence of these derivatives on the metabolic activity of various cancer cell lines was assessed, with IC50 values determined via MTT assays. Notably, derivatives containing ester functional groups exhibited exceptional activity against all tested cancer cell lines, boasting IC50 values below 10 μM. Particularly striking were the spiro derivatives with methoxy groups at position 3 and nitro groups at position 4 of the phenyl ring. These compounds displayed remarkable selectivity and exhibited heightened activity against HCT-116 and Jurkat cell lines. Additionally, 4-oxo-1,3-thiazolidin-2-ylidene derivatives demonstrated a significant activity against MCF-7 and HCT-116 cancer cell lines.

Two tetranuclear [Zn4Cl2(ClQ)6]·2DMF (1) and [Zn4Cl2(ClQ)6(H2O)2]·4DMF (2), as well as three dinuclear [Zn2(ClQ)3(HClQ)3]I3 (3), [Zn2(dClQ)2(H2O)6(SO4)] (4) and [Zn2(dBrQ)2(H2O)6(SO4)] (5), complexes (HClQ = 5-chloro-8-hydroxyquinoline, HdClQ = 5,7-dichloro-8-hydroxyquinoline and HdBrQ = 5,7-dibromo-8-hydroxyquinoline) were prepared as possible anticancer or antimicrobial agents and characterized by IR spectroscopy, elemental analysis and single crystal X-ray structure analysis. The stability of the complexes in solution was verified by NMR spectroscopy. Antiproliferative activity and selectivity of the prepared complexes were studied using in vitro MTT assay against the HeLa, A549, MCF-7, MDA-MB-231, HCT116 and Caco-2 cancer cell lines and on the Cos-7 non-cancerous cell line. The most sensitive to the tested complexes was Caco-2 cell line. Among the tested complexes, complex 3 showed the highest cytotoxicity against all cell lines. Unfortunately, all complexes showed only poor selectivity to normal cells, except for complex 5, which showed a certain level of selectivity. Antibacterial potential was observed for complex 5 only. Moreover, the DNA/BSA binding potential of complexes 1–3 was investigated by UV-vis and fluorescence spectroscopic methods.