Docking assisted design of novel 4-adamantanyl-2-thiazolylimino-5-arylidene-4-thiazolidinones as potent NSAIDs.

Docking analysis was used to predict the effectiveness of adamantanyl insertion in improving cycloxygenase/lipoxygenase (COX/LOX) inhibitory action of previously tested 2-thiazolylimino-5-arylidene-4-thiazolidinones. The crystal structure data of human 5-LOX (3O8Y), ovine COX-1 (1EQH) and mouse COX-2 (3ln1) were used for docking analysis. All docking calculations were carried out using AutoDock 4.2 software. Following prediction results, 11 adamantanyl derivatives were synthesized and evaluated for biological action. Prediction evaluations correlated well with experimental biological results. Comparison of the novel adamantanyl derivatives with the 2-thiazolylimino-5-arylidene-4-thiazolidinones previously tested showed that insertion of the adamantanyl group led to the production of more potent COX-1 inhibitors, as well as LOX inhibitors (increased activity from 200% to 560%). Five compounds out of the 11 exhibited better activity than naproxen; while nine out of 11 showed better activity than NDGA and seven compounds possessed better anti-inflammatory activity than indomethacin.

Serum antioxidant status among young, middle-aged and elderly people before and after antioxidant rich diet.

BACKGROUND: The influence of factors such as age, sex, life style and smoking on oxidative stress status of the organism remains unclear. There is evidence that dietary intake of antioxidants is thought to enforce the organism ability to counteract free radicals. Administration of synthetic antioxidants as dietary supplements does not seem to have the same beneficial effect as consumption of the same antioxidants as part of food ingredients. This work focuses on the investigation of age and diet effects on oxidative stress and examines the hypotheses of their significant influence. METHODS: Blood samples of 146 volunteers, were collected and allocated in three age groups. All volunteers completed a questionnaire concerning home and working environmental conditions, special habits and dietary preferences. We implemented a thirty days diet rich in antioxidants in 55 volunteers. Antioxidant activity was estimated before and after the special diet by measuring the influence of serum in oxidation of ABTS by the ferryl myoglobinhydrogen peroxide system. RESULTS: Our findings showed unexpected lower serum total antioxidant capacity (TAC) in younger people (ages 18-35 yrs) 79%, compared to middle aged and elderly individuals and a large increase 62% in serum TAC of all age-groups after the one-month special diet. CONCLUSION: These results imply that a diet rich in antioxidants based on antioxidant rich food consumption and not on single antioxidants administration, can increase the antioxidant status of the organism and offer better health. The total serum antioxidant status increases with age and this fact should be taken into account when TAC is measured in different diseases.