Agata Kochman

Evidence for antiradical and antioxidant properties of four biologically active N,N-Diethylaminoethyl ethers of flavaone oximes: A comparison with natural polyphenolic flavonoid rutin action

The antiradical and antioxidant activities of four biologically active N,N‐diethyloaminoethyl ethers of flavanone oximes (N,N‐DEAEFo) were investigated in vitro and compared with these of polyphenolic flavonoid (rutin). Four experimental models were used: iron‐ and ascorbate driven Fenton systems, γ‐radiolysis, xanthine/xanthine oxidase system and diphenylpicrylhydrazyl (DPPH) radical scavenging. The results clearly indicate that N,N‐DEAEFo are acting as promising antioxidants and radioprotectors comparable to rutin activities: they should prove to be useful under acute oxidative stress conditions for which both properties were required.

Juvenile hormone binding protein traffic - Interaction with ATP synthase and lipid transfer proteins.

Juvenile hormone (JH) controls insect development, metamorphosis and reproduction. In insect hemolymph a significant proportion of JH is bound to juvenile hormone binding protein (JHBP), which serves as a carrier supplying the hormone to the target tissues. To shed some light on JHBP passage within insect tissues, the interaction of this carrier with other proteins from Galleria mellonella (Lepidoptera) was investigated. Our studies revealed the presence of JHBP within the tracheal epithelium and fat body cells in both the membrane and cytoplasmic sections. We found that the interaction between JHBP and membrane proteins occurs with saturation kinetics and is specific and reversible. ATP synthase was indicated as a JHBP membrane binding protein based upon SPR-BIA and MS analysis. It was found that in G. mellonella fat body, this enzyme is present in mitochondrial fraction, plasma membranes and cytosol as well. In the model system containing bovine F(1) ATP synthase and JHBP, the interaction between these two components occurs with K(d)=0.86 nM. In hemolymph we detected JHBP binding to apolipophorin, arylphorin and hexamerin. These results provide the first demonstration of the physical interaction of JHBP with membrane and hemolymph proteins which can be involved in JHBP molecule traffic.

Synthesis and Antioxidant Activity Evaluation of Novel Antiparkinsonian Agents, Aminoadamantane Derivatives of Nitroxyl Free Radical

Two new analogues of the antiparkinsonian drug 1-aminoadamantane: 4-(1-adamantylamino)-2,2,6,6-tetramethylpiperidine-1-oxyl and 4-(1-adamantylammonio)-1-hydroxy-2,2,6,6-tetramethylpiperidinium dihydrochloride have been synthesized. Their antioxidant activity towards reactive oxygen species (ROS: (z.rad;)OH and O(2)(z.rad;-)) have been evaluated in three test systems. The compound with nitroxide substituent displays higher anti-oxidative capacity than those containing hydroxylamine. The in vivo study of ROS-involving 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-rat model of induced parkinsonism was undertaken to ascertain the neuroprotective ability of the novel synthesized compounds-antioxidants. The data clearly shows that the nitroxide free radical moiety of the molecule is necessary for their neuroprotective action on dopaminergic neurons under the applied conditions of deep oxidative stress caused by the neurotoxin (MPTP). The new synthesized analogues may find application in treatment of parkinsonian syndromes, either to block or to reduce the ROS-mediated neuronal damage and death.

Rutoxyl [rutin/4‐acetamide‐1‐hydroxy‐2,2,6,6‐tetramethylpiperidinium] is a new member of the class of semi‐natural products of high pharmacological potency

A novel complex, Rutoxyl [rutin/4‐acetamide‐1‐hydroxy‐2,2,6,6‐tetramethyl‐piperidinium] was synthesized and its structure and anticancer activity were investigated. The results reported here are consistent with our idea, that the formation of such a complex of two biologically active molecules: polyphenolic flavonoid antioxidant (Rutin) and nitroxylamine of nitroxide antioxidant (Tempace), stabilized by hydrogen bond(s) can result in a supra‐additive properties.