A. E. Prosenko

Synthesis and antioxidant activity of 3,5-dimethyl-4-hydroxybenzylthiododecane

The new multifunctional antioxidant 3,5-dimethyl-4-hydroxybenzylthiododecane (DHBD) demonstrated high activity both in vitro and in vivo. Experiments in vitro showed that the antioxidant activity of DHBD significantly exceeded that of the well-known reference drug ionol. A course of DHBD administration (100 mg/kg, p.o.) significantly decreased the content of lipid peroxidation products in rat brain on the model of long-term incomplete cerebral ischemia.

Synthesis and hepatoprotector activity of water-soluble derivatives of aminoalkylphenols

A series of 2(4)-hydroxybenzyl-and 3-(4-hydroxyaryl)propylamines and their hydrochlorides were synthesized based on 2,4-and 2,6-alkylsubstituted phenols. The synthesized hydrophilic derivatives are characterized by average half-lethal doses (LD50), which fall within 50–170 mg/kg for intraperitoneal administration in mice. Some of the synthesized compounds in a dose of 0.1LD50 show pronounced hepatoprotector activity with respect to tetrachloromethane-induced model toxic hepatitis in mice.

Effect of 3-(3'-tert-butyl-4'-hydroxyphenyl)propyl thiosulfonate sodium on expression of GSTP1 and NQO1 genes and protein transcription factors in BALB/c mouse liver.

The study examined dynamics of the effect of novel phenol antioxidant preparation 3-(3’-tertbutyl- 4’-hydroxyphenyl)propyl thiosulfonate sodium (TS-13) on expression of antioxidant protection enzymes genes GSTP1 and NQO1 and on the content of protein transcription factors NF-κB and ATF-2 in mouse liver. Expression of GSTP1 gene decreased significantly on days 4 and 7 after per os administration of TS-13 (100 mg/kg), but increased on post-administration day 14. On days 7 and 14 post-administration, expression of NQO1 gene was significantly increased. On day 7, the hepatic content of the phosphorylated form of ATF-2 and two subunits of nuclear factor NF-κB (p50, p65) decreased significantly.

Effect of Phenol Inducing the Antioxidant Responsive Element on Drosophila Melanogaster Lifespan

The effect of hydrophilic synthetic antioxidant TC-13 (3-(3’-tert-butyl-4’-hydroxyphenyl) propylthiosulfonate sodium) inducing the antioxidant-responsive element on the lifespan of Drosophila melanogaster was studied. Addition of 1% TC-13 to diets prolonged the lifespan of long-lived D. melanogaster Canton S strain females and males, but not of short-lived Oregon R insects and reduced the mean lifespan of D. melanogaster males of the lgl558OR/Cy strain containing a recessive lethal mutation of tumor suppressor in the heterozygotic state. The geroprotective effects of TC-13 synthetic phenol antioxidant depended on D. melanogaster genotype and gender.

Combination of Methods for in Vitro Study of Antioxidant Properties of Chemical Compounds

We proposed a combination of methods to study antioxidant properties of compounds, including evaluation of the capacity of the test preparations to inhibit peroxidation of unsaturated lipids (in model systems with oxidation of ethyl oleate; aqueous emulsion medium) and low-density lipoproteins (in the presence of transition metal ions), generation of superoxide anion radical (system of lucigenin, xanthine oxidase, and xanthine) and NO·/ONOO— (system of SIN-1 and lucigenin), and induction of respiratory burst in blood granulocytes (luminol-induced and lucigenin-induced reaction after zymosan stimulation). In vitro study showed that the antioxidant properties of synthetic watersoluble phenols depend strongly on masking of the phenol OH group and nature of the ionogenic fragment in the p-propyl substituent.

Antioxidant and Hepatoprotector Activity of Water-Soluble 4-Propylphenols Containing Hydrophilic Groups in Alkyl Chains

One of the main mechanisms in the pathogenesis of toxic liver damage is destabilization of the membranes of hepatocytes as a result of lipid peroxidation (LPO). In the case of such liver disorders, a pronounced protective action is offered by phenolic antioxidants such as -tocopherol [1], potassium phenosane, synthetic derivatives of hydroxycynnamic acids, ionol, ubiquinone, and some other natural compounds [2]. According to [3], some derivatives of hydroxycynnamic acids are superior to -tocopherol with respect to hepatoprotector action. The high hepatoprotector activity of hydroxycynnamic acid derivatives can be due to their hydrophilicity, which accounts for the high rate of transport and biological accessibility of these molecules. Below we report on a comparative study of the antioxidant activity and hepatoprotector properties of a series of water-soluble 2,6-di-tert-butyl-4-propylphenol derivatives (I – IV) and some analogous compounds (V – VIII) not containing tert-butyl groups.

Structural and Functional Characteristics for the Antiinflammatory Effect of New Water-Soluble Sulfur-Containing Phenol Antioxidants

Structurally related phenols containing the p-alkylthiosulfonate substituent and partially hindered by tert-butyl groups were synthesized for the search and development of new synthetic antioxidant, which would be effective in vivo in preventing free radicalinduced pathological processes. Sodium 3-(3-tert-butyl-4-hydroxyphenyl)propylthiosulfonate had high antiinflammatory activity and produced a dose-dependent effect (IC50=36 mg/kg). Changes in the length of the carbohydrate chain in the p-alkyl substituent had no effect on in vitro antiradical activity of the test compounds. However, the decrease in the length of this chain by one methylene unit was accompanied by reduction of antiinflammatory activity of the end product. Lengthening of the chain did not modulate these properties.

Synthesis of S-Alkylisothiuronium Halides by Reaction of Thiourea with ω-(4-Hydroxyaryl)alkyl Halides

A number of new S-alkylisothiuronium salts were synthesized by reaction of ω-[4-hydroxy(methoxy)aryl]alkyl halides with thiourea. The resulting isothiuronium salts in aqueous solution react with sodium (potassium) halides to form halogen exchange products.

Synthesis and Antioxidant Activity of New Water-Soluble 3-(4′-Hydroxyphenyl)propylisothiuronium And Ammonium Salts

Most of the phenolic antioxidants currently used in medicine (vitamin E, ubiquinone, probucol) belong to lipophilic compounds, while the number of known water-soluble drug forms is very restricted. However, the lipophilic character of phenolic antioxidants reduces the velocity of their transport in the organism and decreases penetration into tissues and cells, which can restrict the drug efficacy in urgent cases of free-radical pathologies such as ischemia reperfusion, radiation damage, acute respiratory distress syndrome, or intoxication with hepatotropic poisons. Moreover, since the oxidation processes in living organisms proceed in both lipid (cell membranes, lipoproteins) and aqueous phases, the most effective approach consists in using a combination of fatand water-soluble antioxidants [1]. This study is devoted to the synthesis and comparative investigation of the antioxidant activity of a series of new water-soluble phenolic compounds, representing 3-(4 -hydroxyaryl)propylisothiuronium chlorides (I) and diethyl[3-(4 -hydroxyaryl)propyl]ammonium chlorides (II):