Synthesis, COX-1/2 inhibition and antioxidant activities of new oxicam analogues designed as potential chemopreventive agents

• DOI: 10.18388/abp.2018_2614
• Publication Date: 2018-06-15T16:37:46Z
• Authors: Berenika Marta Sz...; Katarzyna Gębczak; Tomasz Gębarowski; Jadwiga Maniewska
• Keywords: 0301 basic medicine; Anti-Inflammatory Agents, Non-Steroidal; Thiazines; Antineoplastic Agents; Chemoprevention; Antioxidants; 3. Good health; Oxidative Stress; Structure-Activity Relationship; 03 medical and health sciences; Cell Line, Tumor; Drug Design; Humans; Cyclooxygenase Inhibitors; Reactive Oxygen Species

Oxicams (e.g. piroxicam, meloxicam) are widely used nonsteroidal anti-inflammatory drugs (NSAIDs). A large body of evidence from epidemiological and preclinical studies has shown that NSAIDs have a chemopreventive effect on different types of cancer, especially in colorectal cancer. Moreover mounting evidence from preclinical and clinical studies suggests that persistent inflammation functions as a driving force in the journey to cancer. What is more, inflammation induces reactive oxygen and nitrogen species, which cause damage to important cellular components (e.g., DNA, proteins and lipids), which can directly or indirectly contribute to malignant cell transformation. In this study, we discuss the synthesis and the resultant newly synthesised oxicam derivatives which are potentially chemopreventive, and at the same time antioxidant. Compound 9c with highest therapeutic index in the LoVo cancer cell line was found to be the most efficient at ROS scavenging activity in the condition of oxidative stress.