A study on the antioxidant activities of some new benzazole derivatives.

The in vitro antioxidant properties of some new benzazole derivatives (1-10) such as benzoxazoles, benzimidazoles, and benzothiazoles were determined by their effects on the rat liver microsomal NADPH-dependent lipid peroxidation (LP) level, the scavenging of superoxide anion and the stable radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). Compounds 1, 2, 4 and 6, showed potent scavenging effect on superoxide radical at 10(-3) M. Compound 8, 5-nitro-2-(phenoxymethyl)benzimidazole, strongly inhibited lipid peroxidation at 10(-3) M concentration.

A study on the antioxidant capacities of some benzimidazoles in rat tissues.

Seven benzimidazole compounds were synthesized and their in vitro effects on rat liver, lung and kidney microsomal NADPH-dependent lipid peroxidation (LP) levels were determined. The significant decrease in male rat liver microsomal LP level was noted only by the compound 4 at 10(-4) M (20%) and 10(-3) M (40%) concentrations whereas the other compounds were ineffective. In lung, only the compound 6 at 10(-4) M concentration exhibited significant alteration, i.e. 56% increase, in LP level. In kidney, however, apart from the compound 4, all the compounds increased LP level (35-52%) significantly. The classical antioxidant, butylated hydroxy toluene (BHT), at 10(-4) M concentration, significantly decreased LP level about 70%, in all the tissues studied. To clarify the effects of compounds 4 and 6 on LP, the responses of some CYPs, which are active in producing reactive oxygen species, to these compounds were also investigated. The compound 4 at 10(-4) and 10(-3) M concentrations inhibited the hepatic microsomal ethoxyresorufin O-deethylase (EROD) (37 and 65%) and pentoxyresorufin O-depenthylase (PROD) (14 and 62%) enzyme activities significantly. However, it did not alter the hepatic microsomal NADPH-cytochrome P450-reductase activity. BHT, at 10(-3) M concentration, significantly inhibited hepatic microsomal EROD (73%), PROD (62%) and NADPH-cytochrome P450 reductase (17%) enzyme activities. Caffeine (10(-3)M) and SKF 525A (10(-3)M), which are specific inhibitors of EROD and PROD enzyme activities, significantly decreased the enzyme activities 33 and 77%, respectively. Caffeine was unable to alter hepatic microsomal NADPH-cytochrome P450 reductase enzyme activity whereas SKF 525A significantly inhibited (80%) it. In lung and kidney, the compound 6 at 10(-4)M concentration significantly increased EROD (44 and 19%) and PROD (103 and 86%) enzyme activities. However, the elevation of PROD enzyme activity in both tissues was observed to be more pronounced than that of EROD enzyme activity. This compound was ineffective on lung and kidney microsomal P450-reductase enzyme activity. These results reveal that the synthesized benzimidazoles have variable tissue dependent in vitro effects on LP due to their distinct effects on CYP activities but not on NADPH-cytochrome P450 reductase activity in rats.

Effects of a benzimidazole compound on monooxygenase activities.

A retinoid-type benzimidazole compound (benzimidazole-tetranaphthalene, BITN) was synthesized and its effects on hepatic cytochrome P450 (CYP) dependent ethoxyresorufin O-deethylase (EROD) and pentoxyresorufin O-depentylase (PROD) enzyme activities were determined in rats in vitro. In vitro addition of BITN in 10(-3) M concentration to the reaction medium caused inhibitions in EROD (94%) and PROD (82%) activities. With the same concentration (10(-3) M) all-trans-retinoic acid (RA) was able to inhibit EROD activity 65% and PROD activity 59% whereas buthylated hydroxytoluen (BHT) inhibited EROD and PROD activities 73% and 62%, respectively. The specific inhibitors of EROD activity (caffeine) and PROD activity (SKF 525A) at 10(-3) M concentration inhibited the corresponding enzymes 33% and 77%, respectively. Thus, these results reveal that the BITN has a stronger inhibitory effect than RA, BHT, caffeine and SKF 525 A on the enzyme activities. Since these enzymes (EROD, CYP 1A1/2 and PROD, CYP2B1) activate polycyclic hydrocarbons, aromatic amines and aliphatic halogenated hydrocarbons to their ultimate mutagenic or carcinogenic forms, and are effective in producing reactive oxygen species such as superoxide, hydroxyl radical and hydrogen peroxide, the new compound, BITN, appears to have a greater anticarcinogenic and antioxidant potential than RA and BHT.

Synthesis and antioxidant properties of some new flavone derivatives on lipid peroxidation in the rat liver.

A series of 2'-, 3'-, 4'- and 6-substituted flavone derivatives was synthesized and their in vitro effects on rat liver microsomal NADPH-dependent lipid peroxidation (LP) levels were determined. Retinoic acid, at 10(-4) M concentration, decreased the LP level by about 34%. A significant decrease in male liver microsomal LP level was noted for the compounds 3d, 1a, 3b and 4b at a concentration of 10(-4) M (100%, 95%, 75% and 62%, respectively).

Synthesis and antioxidative properties of novel thiazolidinedione/imidazolidinedione compounds as retinoids.

The general term "retinoids" refers to both naturally occurring as well as synthetic compounds which exhibit biological activity similar to vitamin A (retinol). Vitamin A and its two metabolites, retinaldehyde and retinoic acid, are fat-soluble unsaturated isoprenoids necessary for the growth, differentiation and maintenance of epithelial tissues. In this study, we have synthesized thiazolidinedione/imidazolidinedione compounds as retinoids. Their in vitro effects on rat liver microsomal NADPH-dependent lipid peroxidation (LP) levels and superoxide anion formation were determined.