Molecular structure-activity relationship study of some non-steroidal antiinflammatory agents using electrostatic potential mapping

A series of 6,11-dihydro-11-oxodibenz[b,e]oxepin-2-acetic acids (DOAA) whic h are known to be anti-inflammatory agents were studied. The geometries of some of the molecules obtained from X-ray crystallography were used in the calculations as such while the geometries of their derivatives were obtaine d by local, partial geometry optimization around the Sites of substitution employing the AMI method, keeping the remaining parts of the geometries the same as those in the parent molecules. Molecular electrostatic potential ( MEP) mapping was performed for the molecules using optimized hybridization displacement charges (HDC) combined with Lowdin charges, as this charge dis tribution has been shown earlier to yield near ab initio quality results. A good correlation has been found between the MEP values near the oxygen ato ms of the hydroxyl groups of the carboxy groups of the molecules and their anti-inflammatory activities. The result is broadly in agreement with the m odel proposed earlier by other authors regarding the structure-activity rel ationship for other similar molecules.