Synthesis, antimicrobial and cytotoxic activities of pyrimidinyl benzoxazole, benzothiazole and benzimidazole.

A variety of pyrimidinyl benzoxazoles, benzothiazoles and benzimidazoles linked by thio, methylthio and amino moieties were prepared and studied their antimicrobial and cytotoxic activities. The compound pyrimidinyl bis methylthio benzimidazole 22 was a potent antimicrobial agent particularly against Staphylococcus aureus (29 mm, MIC 12.5 µg/mL) and Penicillium chrysogenum (38 mm, MIC 12.5 µg/mL). The amino linked pyrimidinyl bis benzothiazole 24 exhibited cytotoxic activity on A549 cells with IC50 value of 10.5 µM.

Cadmium and mercury-induced hyperglycemia in the fresh water crab, Oziotelphusa senex senex: involvement of neuroendocrine system.

The effect of exposure to sublethal concentrations of cadmium chloride and mercuric chloride on hemolymph glucose levels of the freshwater crab, Oziotelphusa senex senex, was studied. Intact crabs exposed to cadmium or mercury exhibited a significant hyperglycemia compared to controls, but no significant differences in hemolymph glucose level were detected among the eyestalkless crabs after exposure to metals, suggesting that the effect of metals could be on the sinus gland in the eyestalks, increasing secretion of the hyperglycemic hormone. To test this hypothesis, eyestalks were collected from control and metal exposed crabs, and tested for hyperglycemic effect and also for the hyperglycemic hormone levels. The levels of hyperglycemic hormone and the hyperglycemic effect were significantly low in the eyestalks collected from metal exposed crabs when compared with eyestalks from control crabs. These results strongly suggest that metals act, at least in part, by triggering the secretion of hyperglycemic hormone from the eyestalk.

Identification and characterization of potential impurities of rabeprazole sodium.

Six impurities in rabeprazole sodium bulk drug substance were detected by a simple isocratic high performance chromatographic method (HPLC) whose area percentage ranged from 0.60 to 1.46%. LC-MS was performed to identify the mass of the impurities. A thorough study was undertaken to characterize these impurities. These impurities were synthesized, subsequently characterized and were co-injected with the sample containing impurities and are found to be matching with the impurities in the sample. Based on their spectral data (IR, NMR and MS), these impurities were characterized as 2-[[[4-(3-methoxypropoxy)-3-methyl-2-pyridinyl] methyl]thio]-1H-benzimidazole (impurity I); 2-[[[4-(3-methoxypropoxy)-3-methyl-2-pyridinyl] methyl] sulfonyl]-1H-benzimidazole (impurity II); 2-[[[4-(3-methoxypropoxy)-3-methyl-2-pyridinyl-1-oxide] methyl] sulfonyl]-1H-benzimidazole (impurity III); 2-[[[4-(3-methoxypropoxy)-3-methyl] pyridin-2-yl]methanesulfinyl]-1-[[4-(3-methoxypropoxy)-3-methyl]pyridin-2-ylmethyl]-1H-benzimidazole (impurity IV); 2-[[[4-methoxy-3-methyl-2-pyridinyl] methyl] sulfinyl]-1H-benzimidazole (impurity V); 2-[[[4-(3-methoxypropoxy)-3-methyl-2-pyridine-1-oxide] methyl] sulfinyl]-1H-benzimidazole (impurity VI).

Alterations in hepatic metabolism of adult male rats following exposure to hydroxyprogesterone during embryonic development.

AIM: To investigate the effect of in utero exposure to hydroxyprogesterone (HP) on liver metabolism in adult male albino rats. METHODS: Pregnant Wistar strain albino rats were exposed to supra-normal levels (10 mg/kg and 25 mg/kg) of HP on days 1, 7 and 14 of pregnancy. The male pups were maintained under controlled conditions and the rats were killed 90 days after birth. The liver tissue was immediately excised, weighed and used for biochemical assays. RESULTS: The activity levels of succinate dehydrogenase (SDH), glutamate dehydrogenase (GDH), glucose-6-phosphate dehydrogenase (G-6-PDH), malate dehydrogenase (MDH) and aminotransaminases were significantly increased in the livers of rats exposed to HP during embryonic development. The lactate dehydrogenase (LDH) activity level was significantly decreased in the liver of experimental rats. Furthermore, there was a significant elevation of activity levels of antioxidant enzymes (glutathione S-transferase [GST] and catalase [CAT]) with an increased lipid peroxidation in the hepatic tissue of experimental rats compared with the control group. CONCLUSION: The results of the present study suggest that there is an increase in the oxidative metabolism, antioxidative mechanism and levels of lipid peroxidation in rats exposed to HP during embryonic development. The increased aminotransaminase activities in these rats reveal tissue damage and disruption of mitochondrial integrity.

Gestational exposure to hydroxyprogesterone caproate suppresses reproductive potential in male rats.

Hydroxyprogesterone caproate was administered to pregnant rats at a dose level of 10 and 25 mg/kg body weight on 1st, 7th and 14th gestational day and the male pups (F1 generation) were allowed to grow for 90 days. The effect of gestational exposure to hydroxyprogesterone caproate on fertility was assessed by breeding F1 male rats with control female rats besides analyzing sperm quality and quantity in F1 male rats. The number of implantation sites and viable fetuses was significantly reduced in females mated with F1 males that were exposed to hydroxyprogesterone caproate during embryonic development. The decrease in sperm function was associated with a decrease in sperm motility, sperm viability and sperm count in F1 rats. The study clearly indicates that in utero exposure to hydroxyprogesterone caproate affects fertility in male rats.

The synthesis and effects of prostaglandins on the ovary of the crab Oziotelphusa senex senex.

The possible involvement of prostaglandins in the regulation of ovarian development in the crab Oziotelphusa senex senex was investigated. Uptake of labelled arachidonic acid into the ovary of the crab was significantly greater than the other tissues. Prostaglandin H synthase activity was significantly increased in the ovary during the late vitellogenic stage when compared to immature ovary. The biosynthesis of different prostaglandins in the ovary was also measured during the crab reproductive cycle. Injection of prostaglandin F(2alpha) and prostaglandin E(2) significantly increased ovarian index and oocyte diameter in a dose-dependent manner. In contrast, injection of prostaglandin D(2) did not affect ovarian growth. These results demonstrate the presence of prostaglandin biosynthetic system in ovary of the fresh water crabs.

Effect of prenatal exposure to hydroxyprogesterone on steroidogenic enzymes in male rats.

Pregnant Wistar strain albino rats were administered hydroxyprogesterone and the steroidogenic potential of the testis was analysed in the next generation adult male rats. In utero exposure to supranormal levels (10 mg/kg body weight or 25 mg/kg body weight) of hydroxyprogesterone decreased the activity levels of marker steroidogenic enzymes (3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase) of adult (mature) rat testis. Hydroxyprogesterone mediation in the suppression of rat testicular steroidogenesis is suggested, which can be correlated to the observed decrease in male reproductive potential in mammals exposed to female hormones during embryonic development.