Study of Cyclooxygenase inhibition by some compounds and plant extracts

Abstract

This study involved preparation a set of amides of anti-inflammatory drugs as well as the identification and characterization of products by FT-IR, 1HNMR and13C NMR spectroscopy, and C.H.N elements data, and preparation some plants extracts. The second part of work include testing the activity of prepared compounds and plant extracts as inhibitors of cyclooxygenase and their selectivity in vivo and by using theoritical programs This work involved: 1. preparations of acid chloride from ibuprofen and anhydrides from naproxen, sodium diclofenac and mefenamic acid and then transferred them to different amides by reacting with different amines (sulphanilamide, O-nitroaniline, 2,4 dinitroaniline, P-bromoaniline) 2. Preparation of anthocyanin extract from red cabbage (Brassica oleracea var. capitata) and The total concentration of anthocyanin was (46 mg \ 100 g) and the extraction of oil from the mint at a yield of 0.4%. 3. The results showed that the prepared compounds and extracts were effective analgesics. Using different doses in mice and in different points in time through the use of heat source give response and measure response time comparing with aspirin and sodium Diclofenac (Voltaren). These results indicate that the compounds are effective inhibitors of cyclooxygenase, because the pain caused by the effectiveness of cyclooxygenase and the most effectiveness compounds were compound [2-(6-methoxynaphthalen-2-yl)-N-(4- sulfamoylphenyl) propanamide] which produced from reaction between naproxen and sulphanilamide and compound [2-(2-(2,6- dichlorophenylamino) phenyl)-N-(4-sulfamoylphenyl)acetamide] which produced from reaction between Diclofenac and sulphanilamide. 4. All prepared compounds and isolated crude extract have been tested clinically using Swiss mice to show their activity as inhibitors against cyclooxygenase by testing their activity as anti-inflammatory in different doses and different times by egg-white induced oedema via determination of percentage of inhibition and compared them with sodium diclofenac and aspirin. It is found that the newly prepared compounds are effective as anti-inflammatory and some of them exceed the effectiveness of Vol.taren. 5. The results showed that all prepared compounds and extracts have analgesic activity by using different doses at different times by hot plate test and determine response time and compared it with sodium diclofenac and aspirin. But the activity were dissimilar. 6. The prepared compounds and extracts are inhibitors of cyclooxygenase, that findings have been proved by estimation the concentration of PGE2 in blood plasma which determined after created inflammation in rats before and after injection of prepared compounds, extracts and the parent compounds comparing the results with the normal level. The results of this experiment showed that some prepared compounds has higher activity of inhibition than the parent medication, and give a good picture of selectivity of inhibition of COX -2 by comparing with celecoxib. 7. One of important results of new prepared compounds were that they do not have ulceration effect on stomach which could be prover through the test of stomach ulcers and the use of high doses on Swiss mice. 8. Through a molecular docking studies of prepared compounds with the active site of the enzyme COX-1 and COX-2 , it was found that the compounds have affinity for the enzyme COX-2 more than their affinity to COX-1 which support selectivity, also it is found that Carvon who constitute more than 50% of mint oil is a selective inhibitor of COX-2.