Novel binuclear copper(II) complexes with sulfanylpyrazole ligands: synthesis, crystal structure, fungicidal, cytostatic, and cytotoxic activity.

New binuclear copper(II) [Cu(II)] tetraligand complexes (six examples) with sulfanylpyrazole ligands were synthesized. Electron spin resonance (ESR) studies have shown that in solution the complexes are transformed to the mononuclear one. Fungicidal properties against Candida albicans were found for the Cu complexes with benzyl and phenyl substituents. An in vitro evaluation of the cytotoxic properties of Cu chelates against HEK293, Jurkat, MCF-7, and THP-1 cells identified the Cu complex with the cyclohexylsulfanyl substituent in the pyrazole core as the lead compound, whereas the Cu complex without a sulfur atom in the pyrazole ligand had virtually no cytotoxic or fungicidal activity. The lead Cu(II) complex was more active than cisplatin. Effect of the S-containing Cu complex on apoptosis and cell cycle distribution has been investigated as well.

Synthesis of fusidane triterpenoid Mannich bases as potential antibacterial and antitumor agents.

Mannich bases (8 examples) were synthesized via aminomethylation of fusidane propargyl esters. In vitro antimicrobial screening against key ESKAPE pathogens showed that the fusidic acid based Mannich products exhibit a high antimicrobial effect against Gram-positive bacteria Staphylococcus aureus and the fungus Cryptococcus neoformans. Moreover, the cytotoxic effect of fusidic acid and its analogs, which showed high antibacterial activity, was determined by MTT assay on cancer HepG2, HCT-116, SH-SY5Y, MCF-7, A549 and conditionally normal cells HEK293. A remarkable cytotoxic activity of fusidic acid propargyl ester and its aminomethylene derivatives against cancer and nontumoral HEK293 cells with IC50 values within 4.2-25 µM was found.