title: Molecular Docking Analysis of Selected Clinacanthus nutans Constituents as Xanthine Oxidase, Nitric Oxide Synthase, Human Neutrophil Elastase, Matrix Metalloproteinase 2, Matrix Metalloproteinase 9 and Squalene Synthase Inhibitors.
abstract: BACKGROUND
  Clinacanthus nutans (Burm. f.) Lindau has gained popularity among Malaysians as a traditional plant for anti-inflammatory activity.
  
  
  OBJECTIVE
  This prompted us to carry out the present study on a selected 11 constituents of C. nutans which are clinacoside A-C, cycloclinacoside A1, shaftoside, vitexin, orientin, isovitexin, isoorientin, lupeol and β-sitosterol.
  
  
  METHODS
  Selected 11 constituents of C. nutans were evaluated on the docking behavior of xanthine oxidase (XO), nitric oxide synthase (NOS), human neutrophil elastase (HNE), matrix metalloproteinase (MMP 2 and 9), and squalene synthase (SQS) using Discovery Studio Version 3.1. Also, molecular physicochemical, bioactivity, absorption, distribution, metabolism, excretion, and toxicity (ADMET), and toxicity prediction by computer assisted technology analyzes were also carried out.
  
  
  RESULTS
  The molecular physicochemical analysis revealed that four ligands, namely clinacoside A-C and cycloclinacoside A1 showed nil violations and complied with Lipinski's rule of five. As for the analysis of bioactivity, all the 11 selected constituents of C. nutans exhibited active score (>0) toward enzyme inhibitors descriptor. ADMET analysis showed that the ligands except orientin and isoorientin were predicted to have Cytochrome P4502D6 inhibition effect. Docking studies and binding free energy calculations revealed that clinacoside B exhibited the least binding energy for the target enzymes except for XO and SQS. Isovitexin and isoorientin showed the potentials in the docking and binding with all of the six targeted enzymes, whereas vitexin and orientin docked and bound with only NOS and HNE.
  
  
  CONCLUSIONS
  This present study has paved a new insight in understanding these 11 C. nutans ligands as potential inhibitors against XO, NOS, HNE, MMP 2, MMP 9, and SQS.
  
  
  CONCLUSIONS
  Isovitexin and isoorientin (Clinacanthus nutans constituent) showed potentials in the docking and binding with all of the six targeted enzymes (xanthine oxidase [XO], nitric oxide synthase [NOS], human neutrophil elastase [HNE], matrix metalloproteinase [MMP 2 and 9], and squalene synthase [SQS])Moreover, clinacoside B (C. nutans constituent) exhibited the least binding energy for the target enzymes except for XO and SQSInterestingly, all of the selected ligands from C. nutans showed the potential to dock and bind with HNE. Abbreviations used: C. nutans: Clinacanthus nutans, XO: Xanthine oxidase, NOS: Nitric oxide synthase, HNE: Human neutrophil elastase, MMP: Matrix metalloproteinase, SQS: Squalene synthase, ADMET: Absorption, Distribution, Metabolism, Excretion, and Toxicity, TOPKAT: Toxicity prediction by the computer assisted technology.
authors.affiliation: Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
authors.forename: Radhakrishnan
authors.initials: R
authors.lastname: Narayanaswamy
authors.affiliation: Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
authors.forename: Azizul
authors.initials: A
authors.lastname: Isha
authors.affiliation: Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia.
authors.forename: Lam Kok
authors.initials: LK
authors.lastname: Wai
authors.affiliation: Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia; Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
authors.forename: Intan Safinar
authors.initials: IS
authors.lastname: Ismail
keywords: Clinacanthus nutans; clinacoside B; cycloclinacoside; isoorientin; isovitexin; shaftoside