Synthesis and Pharmacological Activity Evaluation of Oxadiazoles Containing Substituted Dihydropyrimidinone and Chloroquinoline Moities

In the present paper, synthesis of new series of 1,3,4oxadiazole derivatives incorporating substituted dihydropyrimidinone and chloroquinoline moieties 4(a-j) has been reported. All the synthesized compounds were characterized by FTIR, 1 H NMR and Mass spectroscopy. The compounds were screened for their in vivo anti-inflammatory activity by the carrageenan induced rat paw edema method and in vitro anti-bacterial activity against some gram positive and gram negative strains of bacteria. This pharmacological activity evaluation revealed that among all the compounds screened, compounds 4c, 4e and 4g were found to have promising antiinflammatory activity. Moreover, compounds 4b, 4c, 4d, 4g and 4j exhibited promising anti-bacterial activity against the selected pathogenic strains of bacteria. INTRODUCTION: Inflammation is a complex defensive mechanism of the body to any noxious stimulus; this process may vary from a localized to a generalized response characterized by the accumulation of fluids and leukocytes leading to edema and pain 1 . Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat the sign and symptoms of inflammation. NSAIDs exert their anti-inflammatory effect mainly through inhibition of cyclooxygenases (COXs), the key enzymes involved in the biosynthesis of prostaglandin from arachidonic acid. There are two COX isoforms COX-1 and COX-2 2, 3 . Constitutive COX-1 is responsible for providing cytoprotection in gastrointestinal (GI) tract whereas inducible COX-2 mediates inflammation. QUICK RESPONSE CODE DOI: 10.13040/IJPSR.0975-8232.4(12).4607-14 Article can be accessed online on: www.ijpsr.com DOI link: http://dx.doi.org/10.13040/IJPSR.0975-8232.4(12).4607-14 However, the chronic use of NSAIDs may elicit marked gastrointestinal (GI) irritation and ulceration due to their unwanted inhibition of the COX-1 enzyme and the desired blockade of the COX-2 enzyme. The recognition of COX-2 as a potential target has influenced the development of drugs that do not cause GI disorders but retain their clinical efficacy as anti-inflammatory agents 4 . 1, 3, 4-oxadiazoles are an important class of heterocyclic compounds with broad spectrum of biological activities. Substituted 1, 3, 4-oxadiazoles have revealed antibacterial, antimycobacterial, antifungal, anti-inflammatory, analgesic, anticonvulsant and anticancer properties 5 . Also the dihydropyrimidinones are known to exhibit a wide range of biological activities such as anti-viral, anti-tumor, anti-oxidant, anti-bacterial and antiinflammatory properties 6, 7 . In addition, dihydropyrimidinones have emerged as potential calcium channel blockers, anticancer, antihypertensive, α-1a–adrenergic antagonists and neuropeptide antagonists 8 .