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.Materials and 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.Conclusion: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.SUMMARY 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

Molecular docking analysis of phytic acid and 4-hydroxyisoleucine as cyclooxygenase-2, microsomal prostaglandin E synthase-2, tyrosinase, human neutrophil elastase, matrix metalloproteinase-2 and -9, xanthine oxidase, squalene synthase, nitric oxide synthase, human aldose reductase, and lipoxygenase inhibitors

“…In the present study, 4-hydroxyisoleucine showed interaction with Arg880, Thr1010, and MOS1328 amino acid residues of XO; this was in good agreement with the previous report. [ 9 ] However, phytic acid fails to dock with the XO might due to the general poor binding phenomenon as reported by Akdogan et al . [ 25 ]…”

“…In the present study, 4-hydroxyisoleucine exhibited interaction with Ala165, His201, and Glu202 amino acid residues of MMP-2 and with Ala189 and Gln227 amino acid residues of MMP-9, respectively, this finding was in good agreement with previous reports. [ 9 23 ] However, phytic acid fails to dock with the MMP-2 and -9 might due to the general poor binding phenomenon as reported by Akdogan et al . [ 25 ]…”

“…XO is the key enzyme which catalyzes the oxidation of hypoxanthine to xanthine and then to uric acid. [ 9 ] XO is another target protein/enzyme which its docking studies and binding free energy calculations showed 4-hydroxyisoleucine having the maximum interaction energy (−29.23 kcal/mol), but phytic acid fails to dock with the XO. Interestingly, 4-hydroxyisoleucine showed interaction with molybdenum-oxygen-sulfur (MOS) complex which is the key component in XO as shown in Table 11 .…”

“…In this section, ligand preparation, target protein identification and preparation, molecular descriptors calculation, absorption, distribution, metabolism, and excretion (ADME), and Toxicity Prediction by Komputer-assisted Technology (TOPKAT) analysis were carried out according to the previously reported method[ 9 ] as briefly stated below.…”

Using molecular docking analysis to discovery Dregea sinensis Hemsl. potential mechanism of anticancer, antidepression, and immunoregulation

“…The molecular docking calculations were performed using the LibDock protocol under the protein-ligand interaction section in Discovery Studio ® 3.1 (Accelrys, San Diego, USA), which the ligand would be structurally rearranged in response to the receptor. Docking was carried out as described elsewhere,[ 23 ] which hinted the target compounds as inhibitors of proteins.…”