Rationalization of physicochemical characters of 1,5-diarylpyrazole analogs as dual (COX-2/LOX-5) inhibitors: a QSAR approach.
Arachidonic acid metabolizing enzymes cyclooxygenases and lipoxygenases lead to the formation of various eicosanoids involved in variety of human diseases, like inflammation, fever, pain, rheumatic and osteoarthritis, etc. Non-steroidal anti-inflammatory drugs are useful tools in the treatment of prostaglandin mediated complications. The development of dual inhibitors may prevent a drift of arachidonic acid metabolism towards the other pathway, leading to potential side effects. Hence emphasis was focused on quantification of structure-activity relationship, with a view to delineating the influence of key COX-2/LOX-5 activity, to explore structural insights to aid the designing of safer dual inhibitors. The quantification of the structural features of 1,5-diarylpyrazole analogs with various biological activities gave some important structural insights, i.e. Hy (hydrophilic factor) and Mor17v (3D molecular representation of structure based on electron diffraction code). These two physicochemical properties may be helpful in development of more selective dual COX-2/LOX-5 inhibitors.
Revathi
S
S
Molecular Modelling Study Group, CADD Laboratory, Department of Pharmacy, Shri G.S. Institute of Technology and Science, 23 Park Road, Indore 452003, India.
Gupta
Arun Kumar
AK
Soni
Love Kumar
LK
Kavitha
S
S
Wagh
R
R
Kaskhedikar
S G
SG
D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D008956:Models, Chemical; D015394:Molecular Structure; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D012044:Regression Analysis
D052246:Cyclooxygenase 2 Inhibitors; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles