Full Length Research Paper
Synthesis and evaluation of chalcone analogues and pyrimidines as cyclooxygenase (COX) inhibitors Syed Nasir Abbas Bukhari1*, Waqas Ahmad1, Adeel Masood Butt1, Naveed Ahmad1, Muhammad Wahab Bin Amjad1, Muhammad Ajaz Hussain2, Viresh H Shah3 and Amit R Trivedi3 1
Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, 50300, Malaysia. 2 Department of Chemistry, University of Sargodha, Sargodha, Pakistan. 2 Department of Chemistry, Saurashtra University, Rajkot- 360 005, Gujarat, India. Accepted 5 March, 2012
A series of chalcone analogues was synthesized and used as precursor for the synthesis of novel series of pyrimidines. Both groups have been evaluated for their effects on the cyclooxygenases (COXs) that are imperative enzymes in the genesis of prostaglandin H2, which is an antecedent for the biosynthesis of prostaglandins, thromboxanes and prostacyclins. The results depicted that chalcones and pyrimidines are very active inhibitors according to the pattern of substitution. Compounds C4, C5, P4 and P5 with methoxylation and nitro substitutions showed best results to inhibit COX-2. Key words: COX inhibitors, chalcones, pyrimidines, anti-inflammatory agents. INTRODUCTION Cyclooxygenases (COXs) are imperative enzymes in the genesis of prostaglandin H2 which is an antecedent for the biosynthesis of prostaglandins, thromboxanes, and prostacyclins (Hamberg et al., 1974). There are two isoforms of COX enzymes: Cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) correspondingly (Fu et al., 1990). The foremost tasks assigned to COX-1 enzyme include the defence of gastric mucosa, platelet aggregation, and renal blood flow while the COX-2 enzyme is inferable and articulated during inflammation, ache and oncogenesis (Smith et al., 1996). As COX-2 plays its role in inflammation and pain, molecules that restrain its enzymatic action would be of remedial worth. It is established that the enzymatic activity of cyclooxygenases is repressed by numerous non-steroidal anti-inflammatory drugs (NSAIDs) (Meade et al., 1993). These drugs comprise aspirin and indomethacin which are non-discriminating and hold back COX-1 and COX-2 together. Aspirin inhibits COX-1 more strappingly than COX-2 and inhibition of COX-1 by aspirin decreases the creation of PGE2 and PGI2 which has an unfavourable ulcerogenic outcome (Allison et al., 1992). Therefore, in the past few years, selective COX-2 inhibitors, that attain the similar anti-inflammatory efficacy like conventional NSAIDs but lessen the risk of superfluous side effects, have been developed. On the other hand, clinical studies have recommended that selective COX-2 inhibitors could source archetypal COXmediated side effects like gastrointestinal damage, amplified systemic blood pressure, and hypersensitivity (De Gaetano et al., 2003).Chalcones play pivotal role in the biosynthesis of flavonoids and isoflavonoids (Avila et al., 2008). Flavonoids are the constituents of daily diet. Chemically, chalcones consist of a three carbon α, βunsaturated carbonyl system. Consequently, these are the condensation moieties of aromatic aldehyde with acetophenones in the attendance of alkali (Nowakowska, 2007). They undergo an assortment of chemical reactions and are useful in synthesis of pyrazoline, isoxazole and a variety of heterocyclic compounds as hexanones. Chalcones play an important role in synthesizing a range of therapeutic compounds. They have shown promising healing efficacy for the treatment of a number of diseases. Chalcone derivatives have
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Bukhari et al.
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