In silico studies of pyrano [2, 3-c] pyrazoles derivatives as cyclooxygenase-2 inhibitiors

Abstract

Non-steroidal anti-inflammatory drugs (NSAID’s) have been used widely from several decades for treatment of analgesia and inflammation. The most widely reported side effect of NSAID's is inflammation of gastric regions, ulceration and kidney problems. These side effects are due to non-selective inhibition of cyclooxygenase-2 over cyclooxygenase-1.Therefore we planned to design a potent cyclooxygenase-2 inhibitor using insilico techniques which may be used as anti-inflammatory and analgesics. In this current study we have chosen Pyrano[2,3-c] pyrazoles as the parent moiety along with several derivatives. These will acts as ligand molecules for computational protocols. The crystalline structure of cyclooxygenase-2 was downloaded from protein database and the pdb code was 1cx2. This will act as target for computational studies. Pyrx software was used for virtual screening of library of derivatives. The molecular docking of potent derivatives were carried using autodock software X:Y:Z (50:26:40). Other insilico properties were calculated using Molinspiration online property calculator, Protox II for structural property calculation and acute oral toxicity determination respectively. Derivatization in the molecule is must for increasing biological potential of parent moiety. The study revealed best molecule that was having potent analgesic and anti-inflammatory activity. Results revealed though the ligand molecule was safe and effective for cyclooxygenase-2 inhibition. The LD50 calculated was found to be 500 mg/kg. Other In silico property were also calculate.