RESUMO
Cyclooxygenases play a vital role in inflammation and are responsible for the production of prostaglandins. Two cyclooxygenases are described, the constitutive cyclooxygenase-1 and the inducible cyclooxygenase-2, for which the target inhibitors are the non-steroidal anti-inflammatory drugs (NSAIDs). Prostaglandins are a class of lipid compounds that mediate acute and chronic inflammation. NSAIDs are the most frequent choices for treatment of inflammation. Nevertheless, currently used anti-inflammatory drugs have become associated with a variety of adverse effects which lead to diminished output even market withdrawal. Recently, more studies have been carried out on searching novel selective COX-2 inhibitors with safety profiles. In this review, we highlight the various structural classes of organic and natural scaffolds with efficient COX-2 inhibitory activity reported during 2011-2021. It will be valuable for pharmaceutical scientists to read up on the current chemicals to pave the way for subsequent research.
RESUMO
Colorectal cancer is one of the most common cancers globally, ranking second for the number of cancer-related deaths. Metastasis has been reported as the main cause of death in patients with colorectal cancer. Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a transcription factor that functions as a tumor suppressor by inhibiting cellular proliferation, migration, and invasion. In our previous efforts to generate natural product-motivated PPAR-γ ligands, the compounds 1 and 2 were obtained. These compounds activated PPAR-γ and inhibited the migration and invasion of HCT116 colorectal cancer cells, and they were also found to inhibit the epithelial-to-mesenchymal transition, which is a key process in cancer metastasis. Compounds 1 and 2 upregulated expression of the epithelial marker (E-cadherin), and downregulated expression of the mesenchymal marker (N-cadherin) and transcriptional factor (Snail). Therefore, the PPAR-γ agonists 1 and 2 could serve as a valuable model for the study on anti-metastatic leads for the treatment of colorectal cancer.