Open Access Open Access  Restricted Access Subscription Access
Open Access Open Access Open Access  Restricted Access Restricted Access Subscription Access

In-Silico Analysis of various Benzilate Derivatives towards Cyclooxygenase-2 Enzyme


Affiliations
1 Department of Chemistry, School of Basic Sciences, Vels Institute of Science, Technology and Advanced Studies, India
2 Department of Bio-Engineering, B.Tech Biotechnology, Vels Institute of Science, Technology and Advanced Studies, India
     

   Subscribe/Renew Journal


Cyclooxygenases (COX-1 and COX-2) catalyze the rate-limiting step in the biosynthesis of prostaglandins, prostacyclins, and thromboxanes. Ibuprofen has classically fallen into the time-dependant class of COX inhibitors as it binds rapidly and reversibly to Cox and acts as a competitive inhibitor of arachidonic acid oxygenation.The discovery of new and novel anti-inflammatory drugs is an area of intense interest in both pharmaceutical industry and academic laboratories. Significant advances have been made in the treatment of inflammatory diseases such as rheumatoid arthritis and multiple sclerosis, but most dramatically with new biologic agents. Perhaps due in part to the mixed experiences with COX-2 inhibitors, very few small molecule anti-inflammatory drugs with novel modes of action have made it to the market in the last decade.The various benzilic acid compounds synthesized have taken for in-silico analysis to study the structure activity relationship using crystal structure co-crystallized with 2-(4-isobtyl phenyl) propionic acid (PDB ID: 4PH9).The synthesized ligands were docked using three different docking strategies; High throughput virtual screening, Standard Precision and Extra Precision docking strategies. After three different analyses, the docking scores of the synthesized compounds were found to be in the range of -8.221 to –6.342 Kcal mol-1. Finally the compounds are shortlisted based on the visual inspection of the amino acids interaction.

Keywords

Cyclooxygenases, Docking, Benzilic Acid and Inflammatory Diseases.
Subscription Login to verify subscription
User
Notifications
Font Size


  • Brindha Devi, Rajagopala K, Esther Elizabeth, Pharmacophoric Screening of Various Endophytic Fungal Metabolites, Asian Journal of Pharmaceutical and Clinical research, 2017;10(5): 140-146.
  • Sudha.R, Charles C Kanakam, Nithya.G, In vitro antioxidant activity of different substituted benzilic acid using DPPH and ABTS assay method, Asian journal of pharmaceutical and clinical research, 2016; 9(3): 127-130.
  • Sudha .R, Charles C Kanakam, Nithya.G, Synthesis, characterization and antimicrobial activity of benzilic acids, International journal of chem.Tech research, 2015;8(10): 383-38.
  • Smith WL, Urade Y, Jakobsson PJ, Enzymes of the cyclooxygenase pathways of prostanoid biosynthesis, Chem Rev, 2011;111(10):5821-65.
  • Maestro, Version 9.3, Schrödinger, LLC, New York, NY, 2016
  • Saxena S, Devi PB, Soni V, Yogeeswari P, Sriram D. Identification of novel inhibitors against Mycobacterium tuberculosis L-alaninedehydrogenase (MTB-AlaDH) through structure-based virtual screening. J Mol Graph Model, 2014; 47: 37-43.
  • Theras P.J, Manvar D, Kondepudi S, Battu M.B, Sriram D, Basu A, Yogeeswari P, Basu N.K, Multiple e-pharmacophoremodelling, 3D-QSAR, and High-Throughput Virtual screening of Hepatitis C Virus NS5B Polymerase Inhibitors, J.Chem.Inf.Model, 2014.;54: 539-55.
  • Nagamani S, Kesavan C, Muthusam K, E-Pharmacophore mapping and docking studies on Vitamin D receptor (VDR), Bioinformation, 2012; 15: 705-710.
  • Friesner RA, Banks JL, Murphy RB, Halgren TA, Klicic JJ, Mainz DT, et al. Glide: A new approach for rapid, accurate docking and scoring. Method and assessment of docking accuracy, J Med Chem, 2004; 47(7):1739-49.
  • Alverez J, Shoichet B. Virtual Screening in Drug Discovery. Boca Raton, Florida: Taylor Francis, 2005.
  • Kawatkar S, Wang H, Czerminski R, Joseph-McCarthy D. Virtual fragment screening: An exploration of various docking and scoring protocols for fragments using Glide. J Computer Aided Mol Des, 2009;23(8):527-39.
  • Sudha.R, Brindhadevi.P, Charles C Kanakam, Nithya.G, Docking studies for various antibacterial benzilate derivatives, Asian Journal of Pharmaceutical and clinical research, 2017;10(4): 268-271.

Abstract Views: 353

PDF Views: 0




  • In-Silico Analysis of various Benzilate Derivatives towards Cyclooxygenase-2 Enzyme

Abstract Views: 353  |  PDF Views: 0

Authors

R. Sudha
Department of Chemistry, School of Basic Sciences, Vels Institute of Science, Technology and Advanced Studies, India
P. Brindha Devi
Department of Bio-Engineering, B.Tech Biotechnology, Vels Institute of Science, Technology and Advanced Studies, India
G. Nithya
Department of Chemistry, School of Basic Sciences, Vels Institute of Science, Technology and Advanced Studies, India

Abstract


Cyclooxygenases (COX-1 and COX-2) catalyze the rate-limiting step in the biosynthesis of prostaglandins, prostacyclins, and thromboxanes. Ibuprofen has classically fallen into the time-dependant class of COX inhibitors as it binds rapidly and reversibly to Cox and acts as a competitive inhibitor of arachidonic acid oxygenation.The discovery of new and novel anti-inflammatory drugs is an area of intense interest in both pharmaceutical industry and academic laboratories. Significant advances have been made in the treatment of inflammatory diseases such as rheumatoid arthritis and multiple sclerosis, but most dramatically with new biologic agents. Perhaps due in part to the mixed experiences with COX-2 inhibitors, very few small molecule anti-inflammatory drugs with novel modes of action have made it to the market in the last decade.The various benzilic acid compounds synthesized have taken for in-silico analysis to study the structure activity relationship using crystal structure co-crystallized with 2-(4-isobtyl phenyl) propionic acid (PDB ID: 4PH9).The synthesized ligands were docked using three different docking strategies; High throughput virtual screening, Standard Precision and Extra Precision docking strategies. After three different analyses, the docking scores of the synthesized compounds were found to be in the range of -8.221 to –6.342 Kcal mol-1. Finally the compounds are shortlisted based on the visual inspection of the amino acids interaction.

Keywords


Cyclooxygenases, Docking, Benzilic Acid and Inflammatory Diseases.

References