Cyclooxygenases are a family of enzymes that play a critical role in regulating inflammation, pain, and fever in the human body. There are two main isoforms of cyclooxygenases, COX-1 and COX- 2, with different roles and expression patterns in various tissues. COX-1 is constitutively expressed in most tissues and plays a crucial role in maintaining homeostasis, while constitutively expressed COX-2 is restricted to specific regions. In addition, COX-2 is an inducible enzyme, expressed at sites of inflammation and cancer Despite their essential functions in the body, cyclooxygenases are also associated with the development of various diseases, including cancer. It has been noted that in several types of tumours, such as colorectal, breast, and lung cancer, there is an increase in the expression of the COX-2 enzyme, which is associated with the development and progression of cancer. The overexpression of COX-2 leads to an increase in prostaglandin production, which promotes tumour growth and angiogenesis, making it an attractive target for cancer therapy.
To study the behaviour of COX-2 in cancerous cells, researchers employed fluorescent compounds derived from known anti-inflammatory drugs. These compounds can differentiate between healthy cells undergoing a common inflammatory process and cancerous cells with an overexpression of the enzyme. Using these fluorescent probes, researchers can study the behaviour of the enzyme and its effect on the surrounding cellular environment. Advanced computational tools, such as hybrid QM/MM molecular dynamics simulations, have been used to simulate the fluorescence spectra of COX-2-specific fluorogenic probe bound to huCOX-2 monomer and dimer. This study aims to investigate the effect of the two types of systems on the fluorescence maxima of the modified drugs. By exploring the relationship between the formation of the huCOX-2 dimer and cancer in more depth, this research sheds light on the behaviour of the protein in cells that are not in homeostasis and present huCOX-2 overexpression. Furthermore, this study provides valuable insights into the design of specific drugs for cancertreatment, which could potentially improve patient outcomes and quality of life.
