Journal
MEDICINAL RESEARCH REVIEWS
Volume 31, Issue 2, Pages 161-201Publisher
WILEY
DOI: 10.1002/med.20182
Keywords
cyclooxygenase; cancer; inflammation; structure-activity relationship; drug development; clinical studies
Categories
Funding
- Ministry of Education, Science and Technology (MEST) of Korea
- MEST [2009-0076697]
- National Research Foundation of Korea [2009-0076697] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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The traditional nonsteroidal anti-inflammatory drugs (NSAIDs) exert their effect by inhibition of cyclooxygenase-1 (COX-1) as well as COX-2 enzymes. As COX-1 is responsible for maintaining normal biological functions, the nonselective inhibition of these enzymes caused side effects including gastrointestinal (GI) problems. Recently developed selective COX-2 inhibitors could reduce these adverse effects, but the evidence of cardiovascular side effects including an increased risk of myocardial infarction began to emerge, and some of the COX-2 inhibitors were eventually withdrawn from the market and this led to the downfall of this research. So, the discovery of novel COX-2 inhibitors with their safety profile became the biggest challenge in pharmaceutical research. However, recent mechanistic and clinical studies revolutionized this area by indicating the fact that COX-2 is involved in apoptosis resistance, angiogenesis, and tumor progression. Epidemiological data suggest that selective COX-2 inhibitors might prevent the development of cancers. Moreover, COX-2 is found to be overexpressed in many cancers thus making it an attractive therapeutic target for the prevention and treatment of a number of malignancies. The purpose of this review is to focus on the medicinal chemistry aspects of COX-2 inhibitors in cancer chemotherapy and recent reports on these inhibitors as anticancer agents. We attempted to cover only the COX inhibitors that showed anticancer activity, although a number of potent COX-2 inhibitors have been reported without their anticancer effects. Furthermore, structure-activity relationships (SAR) of different classes of compounds for COX-2 inhibition as well as anticancer activity, and their future applications are discussed. (C) 2009 Wiley Periodicals, Inc. Med Res Rev, 31, No. 2, 161-201, 2011
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