| Autor: |
Occhiuzzi MA; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy., Ioele G; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy., De Luca M; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy., Rizzuti B; CNR-NANOTEC, SS Rende (CS), Department of Physics, University of Calabria, Via Pietro Bucci, 87036 Rende, CS, Italy.; Institute of Biocomputation and Physics of Complex Systems (BIFI), Joint Unit GBsC-CSIC-BIFI, University of Zaragoza, 50018 Zaragoza, Spain., Scordamaglia D; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy., Lappano R; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy., Maggiolini M; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy., Garofalo A; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy., Grande F; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, CS, Italy. |
| Abstrakt: |
Arylalkane-derived prodrugs of arylacetic acids are a small group of substances that have long been known for their anti-inflammatory action. Despite their ease of synthesis and good potential for the development of new potent and safe anti-inflammatory agents, this group of substances has not received much attention from researchers so far. Therefore, representative arylalkane derivatives were investigated through molecular docking techniques to verify the possible hepatic activation mode toward active metabolites by CYP1A2. In this regard, arylalkanoic acid prodrugs were docked with a crystallographic structure of human CYP1A2, in which the enzyme is co-crystallized with the selective competitive inhibitor α-naphthoflavone BHF. Of note, all the examined compounds proved capable of interacting with the enzyme active site in a manner similar to Nabumetone, thus confirming that a productive metabolic transformation is feasible. On the basis of these findings, it is possible to argue that subtle differences in the way CYP1A2 accommodates the ligands depend on the fine details of their molecular structures. Overall, these data suggest that compounds simply formed by an aromatic moiety bearing an appropriate alkane-derived chain could lead to innovative anti-inflammatory agents. |
