1. Synthesis, COX-1/2 inhibition and antioxidant activities of new oxicam analogues designed as potential chemopreventive agents
- Author
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Berenika Szczęśniak-Sięga, Tomasz Gębarowski, Jadwiga Maniewska, and Katarzyna Gębczak
- Subjects
0301 basic medicine ,Antioxidant ,medicine.medical_treatment ,Thiazines ,Antineoplastic Agents ,Inflammation ,Pharmacology ,Piroxicam ,medicine.disease_cause ,Chemoprevention ,Antioxidants ,General Biochemistry, Genetics and Molecular Biology ,Structure-Activity Relationship ,03 medical and health sciences ,Therapeutic index ,Cell Line, Tumor ,medicine ,Humans ,Cyclooxygenase Inhibitors ,Chemistry ,Anti-Inflammatory Agents, Non-Steroidal ,Cancer ,medicine.disease ,Oxidative Stress ,Meloxicam ,030104 developmental biology ,Drug Design ,Oxicam ,medicine.symptom ,Reactive Oxygen Species ,Oxidative stress ,medicine.drug - Abstract
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.
- Published
- 2018