Kinetin (N6-furfuryladenine) belongs to a group of plant growth hormones involved in cell division, differentiation and other physiological processes. One of the possible ways to obtain biologically active compounds is to complex biologically relevant natural compounds to suitable metal atoms. In this work, two structural groups of Zn(II) complexes [Zn(L(n))2Cl2]·Solv (1-5) and [Zn(HL(n))Cl3] · xL(n) (6-7); n=1-5, Solv=CH3OH for 1 and 2H2O for 2; x =1 for 6 and 2 for 7; involving a phytohormone kinetin and its derivatives (L(n)) were evaluated for their ability to modulate secretion of tumour necrosis factor (TNF)-α, interleukin (IL)-1β and matrix metalloproteinase (MMP)-2 in a lipopolysaccharide (LPS)-activated macrophage-like THP-1 cell model. The penetration of the complexes to cells was also detected. The mechanism of interactions of the zinc(II) complexes with a fluorescent sensor N-(6-methoxy-8-quinolyl)-p-toluene sulphonamide (TSQ) and sulfur-containing biomolecules (l-cysteine and reduced glutathione) was studied by electrospray-ionization mass spectrometry and flow-injection analysis with fluorescence detection. The present study showed that the tested complexes exhibited a low cytotoxic effect on the THP-1 cell line (IC50>40 µM), apart from complex 4, with an IC50=10.9 ± 1.1 µM. Regarding the inflammation-related processes, the Zn(II) complexes significantly decreased IL-1β production by a factor of 1.47-2.22 compared with the control (DMSO), but did not affect TNF-α and MMP-2 secretions. However, application of the Zn(II) complexes noticeably changed the pro-MMP-2/MMP-2 ratio towards a higher amount of maturated MMP-2, when they induced a 4-times higher production of maturated MMP-2 in comparison with the vehicle-treated cells under LPS stimulation. These results indicated that the complexes are able to modulate an inflammatory response by influencing secretion and activity of several inflammation-related cytokines and enzymes.

• MeSH
• Macrophage Activation drug effects   MeSH
• Aminoquinolines MeSH
• Anti-Inflammatory Agents chemical synthesis   pharmacology   MeSH
• Biological Transport MeSH
• Chlorides chemistry   MeSH
• Cysteine chemistry   MeSH
• Gene Expression drug effects   MeSH
• Fluorescent Dyes MeSH
• Glutathione chemistry   MeSH
• Interleukin-1beta antagonists & inhibitors   genetics   metabolism   MeSH
• Cations, Divalent MeSH
• Kinetin chemistry   MeSH
• Coordination Complexes chemical synthesis   pharmacology   MeSH
• Humans MeSH
• Lipopolysaccharides pharmacology   MeSH
• Macrophages cytology   drug effects   metabolism   MeSH
• Matrix Metalloproteinase 2 genetics   metabolism   MeSH
• Cell Line, Tumor MeSH
• Tumor Necrosis Factor-alpha genetics   metabolism   MeSH
• Tosyl Compounds MeSH
• Cell Survival drug effects   MeSH
• Zinc chemistry   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Aminoquinolines MeSH
• Anti-Inflammatory Agents MeSH
• Chlorides MeSH
• Cysteine MeSH
• Fluorescent Dyes MeSH
• Glutathione MeSH
• Interleukin-1beta MeSH
• Cations, Divalent MeSH
• Kinetin MeSH
• Coordination Complexes MeSH
• Lipopolysaccharides MeSH
• Matrix Metalloproteinase 2 MeSH
• N-(6-methoxy-8-quinolyl)-4-toluenesulfonamide MeSH Browser
• Tumor Necrosis Factor-alpha MeSH
• Tosyl Compounds MeSH
• Zinc MeSH