Molecular docking for identification of novel potential COX inhibitors of some isolated compounds from Clausena lansium for analgesic treatment Mohammad Shah Hafez Kabir1,4, Arkajyoti Paul2,4*, Md. Mominur Rahman1,4, Mir Muhammad Nasir Uddin3, Abul Hasanat1,4, Mohammed Shoibe1,4, Mohuya Majumder2,4, Md. Golamur Rahman2, Joy Chakraborty2,4 1 Department of Pharmacy, International Islamic University Chittagong, Chittagong, Bangladesh, 2Department of Pharmacy, BGC Trust University Bangladesh, Chittagong, Bangladesh, 3Department of Pharmacy, University of Chittagong, Chittagong-4331, Bangladesh, 4 GUSTO Research Group , Chittagong, Bangladesh Abstract RESULTS Developing a new agent in the analgesic field, plants secondary metabolites can be a good source for the Non-Steroidal Antiinflammatory Drugs (NSAID) drug development. For this purpose we subjected the active compounds Clausena lansium of to reveal its potentiality by molecular docking analysis to find out its potent compound against COX-1 and COX-2 which was done by Maestro v 10.1 (Schrodinger) docking analysis. Docking studies by Maestro v 10.1 (Schrodinger) showed that Murrayanine and Clausenaline E of Clausena lansium had the lowest docking score respectively against the COX-1 and COX2 which are -6.471 and -8.325 . Murrayanine and Clausenaline E from Clausena lansium detected with significant docking score which may be a potent analgesic compound because the less docking score, the compound will be more potent. Table 1: Docking score of different compounds with the receptors. Compounds claulamines E clausemarin B Clausenaline C Clausenaline E Murrayanine vanillic acid Xanthotoxol Docking Score with COX 1 -5.252 -5.958 -5.477 -6.412 -6.471 -4.702 -6.336 Docking Score with COX 2 -6.93 -6.479 -8.325 -7.828 -6.592 -7.458 MATERIALS AND METHODS Protein Preparation Three dimensional crystal structure of COX 1 (PDB id:2OYE) and COX 2 (PDB id:6COX) was downloaded in pdb format from the protein data bank. After that, structure was prepared and refined using the Protein Preparation Wizard of Schrödinger-Maestro v10.1. Charges and bond orders were assigned, hydrogens were added to the heavy atoms, selenomethionines were converted to methionines and all waters were deleted. Using force field OPLS_2005, minimization was carried out setting maximum heavy atom RMSD (root-meansquare-deviation) to 0.30 Å. Ligand Preparation Compounds were retrieved from Pubchem databases, i.e. claulamines E, clausemarin B, Clausenaline C, Clausenaline E, Murrayanine, vanillic acid and Xanthotoxol. Glide Standard Precision (SP) ligand docking SP flexible ligand docking was carried out in Glide of SchrödingerMaestro v10.1within which penalties were applied to non-cis/trans amidebonds. Van der Waals scaling factor and partial charge cutoff was selected to be 0.80 and 0.15, respectively for ligand atoms. Final scoring was performed on energy-minimized poses and displayed as Glide score. The best docked pose with lowest Glide score value was recorded for each ligand. Ligand based ADME/Toxicity prediction This analysis is done by following server, •http://www.scfbioiitd.res.in/software/drugdesign/lipinski.jsp#anchort ag •https://ilab.acdlabs.com/iLab2/index.php •http://www.molinspiration.com/cgi-bin/properties Figure: Docking figure of compounds with the receptors. Table 2: ADME/T Properties of Palmitic acid, Carvacrol, Stearic acid, Vicenin. Name of molecules Claulamines E MWα Clausemarin B 335 HB donorβ 2 HB acceptor€ 4 404 1 5 Log P¥ Molar Refractivityµ 4.060449 95.428986 4.741090 118.817764 Clausenaline C 225 1 2 1.802800 58.026188 Clausenaline E 225 1 2 1.802800 58.026188 Murrayanine 225 1 2 1.878820 56.704193 Vanillic acid 167 0 4 0.621940 34.646000 Xanthotoxol 202 0 4 1.055020 42.771999 αMolecular mass less than 500 Dalton lipophilicity (expressed as LogP less than 5) €Less than 5 hydrogen bond donors ¥Less than 10 hydrogen bond acceptors µ Molar refractivity should be between 40-130 βHigh CONCLUSION Docking studies by Maestro v 10.1 (Schrodinger) showed that Murrayanine and Clausenaline E of Clausena lansium had the lowest docking score respectively against the COX-1 and COX2 which are 6.471 and -8.325 . Murrayanine and Clausenaline E from Clausena lansium detected with significant docking score which may be a potent analgesic compound because the less docking score, the compound will be more potent. REFERENCES •Ahmed B, Ashfaq UA, ul Qamar MT, Ahmad M: Anticancer potential of phytochemicals against breast cancer: Molecular docking and simulation approach. Bangladesh Journal of Pharmacology 2014, 9(4):545-550. •Friesner RA, Banks JL, Murphy RB, Halgren TA, Klicic JJ, Mainz DT, Repasky MP, Knoll EH, Shelley M, Perry JK: Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. Journal of medicinal chemistry 2004, 47(7):1739-1749. •Friesner RA, Murphy RB, Repasky MP, Frye LL, Greenwood JR, Halgren TA, Sanschagrin PC, Mainz DT: Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. Journal of medicinal chemistry 2006, 49(21):6177-6196. 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