Molecular docking analysis of curcumin analogues as human neutrophil elastase inhibitors

Narayanaswamy, Radhakrishnan; Lam, Kok Wai; Abas, Faridah; Ismail, Intan Safinar

doi:10.3329/bjp.v9i1.17474

Cited by 10 publications

(10 citation statements)

References 31 publications

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“…In the present study, both ligands showed interaction with Ser195 amino acid residue of HNE; this was good in agreement with previous reports. [ 23 24 ]…”

Section: Resultsmentioning

confidence: 99%

“…MMPs are a group of zinc-dependent endopeptidase which is capable of degrading ECM components, and among the MMPs family, MMP-2 and -9 were reported to be elevated in the pathological conditions such as inflammation, wound healing, cancer, and aging. [ 24 ] The docking studies and binding free energy reported in Table 9 show that 4-hydroxyisoleucine had the highest interaction energy (−43.47 kcal/mol) with that of MMP-2, but phytic acid fails to dock with the MMP-2. 4-hydroxyisoleucine showed interaction with Ala165, His201, and Glu202 amino acid residues of MMP-2 as shown in Table 9 .…”

Section: Resultsmentioning

confidence: 99%

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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

Narayanaswamy¹,

Lam²,

Esa³

2017

Phcog Mag

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Background:The phytoconstituents phytic acid and 4-hydroxyisoleucine have been reported to posses various biological properties.Objective:This prompted us to carry out the docking study on these two ligands (phytic acid & 4-hydroxyisoleucine) against eleven targeted enzymes.Materials and Methods:Phytic acid & 4-hydroxyisoleucine were evaluated on the docking behaviour of cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-2 (mPGES-2), tyrosinase, human neutrophil elastase (HNE), matrix metalloproteinase (MMP 2 and 9), xanthine oxidase (XO), squalene synthase (SQS), nitric oxide synthase (NOS), human aldose reductase (HAR) and lipoxygenase (LOX) using Discovery Studio Version 3.1 (except for LOX, where Autodock 4.2 tool was used).Results:Docking and binding free energy analysis revealed that phytic acid exhibited the maximum binding energy for four target enzymes such as COX-2, mPGES-2, tyrosinase and HNE. Interestingly, we found that 4-hydroxyisoleucine has the potential to dock and bind with all of the eleven targeted enzymes.Conclusion:This present study has paved a new insight in understanding 4-hydroxyisoleucine as potential inhibitor against COX-2, mPGES-2, tyrosinase, HNE, MMP 2, MMP 9, XO, SQS, NOS, HAR and LOX.SUMMARY 4-hydroxyisoleucine has the potential to dock and bind with all 11targeted enzymes such as (cyclooxygenase-2 [COX-2], microsomal prostaglandin E synthase-2 [mPGES-2], tyrosinase, human neutrophil elastase [HNE], matrix metalloproteinase [MMP-2 and -9], xanthine oxidase, squalene synthase, nitric oxide synthase, human aldose reductase, and lipoxygenase)Moreover, docking studies and binding free energy calculations revealed that phytic acid exhibited the maximum binding energy for four target enzymes such as COX-2, mPGES-2, tyrosinase, and HNE; however, for other six target enzymes, it fails to dock. Abbreviations used: COX-2: Cyclooxygenase-2, mPGES-2: Microsomal prostaglandin E synthase-2, HNE: Human neutrophil elastase, MMP-2 and -9: Matrix metalloproteinase-2 and -9, XO: Xanthine oxidase, SQS: Squalene synthase, NOS: Nitric oxide synthase, HAR: Human aldose reductase, LOX: Lipoxygenase, ADME: Absorption, distribution, metabolism, and excretion, TOPKAT: Toxicity Prediction by Computer-assisted Technology.

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“…In the present study, both ligands showed interaction with Ser195 amino acid residue of HNE; this was good in agreement with previous reports. [ 23 24 ]…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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

Narayanaswamy¹,

Lam²,

Esa³

2017

Phcog Mag

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“…Absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction is an important tool for compound selection and prioritization in rational drug design. The information helps reduce the time and computational cost of screening compound libraries to select compounds feasible for synthesis and further testing [ 23 , 24 ]. The results are presented in Table 4 .…”

Section: Resultsmentioning

confidence: 99%

Hits-to-Lead Optimization of the Natural Compound 2,4,6-Trihydroxy-3-geranyl-acetophenone (tHGA) as a Potent LOX Inhibitor: Synthesis, Structure-Activity Relationship (SAR) Study, and Computational Assignment

Rullah

Abas

et al. 2018

Molecules

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A new series of 2,4,6-trihydroxy-3-geranyl-acetophenone (tHGA) analogues were synthesized and evaluated for their lipoxygenase (LOX) inhibitory activity. Prenylated analogues 4a–g (half maximal inhibitory concentration (IC50) values ranging from 35 μM to 95 μM) did not exhibit better inhibitory activity than tHGA (3a) (IC50 value: 23.6 μM) due to the reduction in hydrophobic interaction when the alkyl chain length was reduced. One geranylated analogue, 3d, with an IC50 value of 15.3 μM, exhibited better LOX inhibitory activity when compared to tHGA (3a), which was in agreement with our previous findings. Kinetics study showed that the most active analogue (3e) and tHGA (3a) acted as competitive inhibitors. The combination of in silico approaches of molecular docking and molecular dynamic simulation revealed that the lipophilic nature of these analogues further enhanced the LOX inhibitory activity. Based on absorption, distribution, metabolism, excretion, and toxicity (ADMET) and toxicity prediction by komputer assisted technology (TOPKAT) analyses, all geranylated analogues (3a–g) showed no hepatotoxicity effect and were biodegradable, which indicated that they could be potentially safe drugs for treating inflammation.

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“…Molecular properties of the ligands docked were calculated by Molinspiration server and the likeliness of drug was checked by Lipinski's Rule of Five. An ideal drug molecule should be having a molecular weight of less than 500, total number of hydrogen bond should not exceed 5, miLogP value and should be less than 5 and the sum of N and O should not be more than 10, (Narayanaswamy 2013).…”

Section: Methodsmentioning

confidence: 99%

In silico approaches for inhibitor designing against Plasmepsin-II of malarial parasite, Plasmodium malariae

Kashyap¹,

Sohpal²,

Mahajan³

2016

Biosci. Biotech. Res. Comm

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Plasmodium malariae is one of the causative agents of the deadly disease, malaria. From past few years, investigators have been vigorously involved in searching for an effective cure for this disease. However, the available drugs have not yet proven to be quite effi cient in its eradication primarily because of the advanced rate of mutation of the parasite. The present study is directed towards fi nding an inhibitor against plasmepsin II, one of the aspartic protease encoded by the malarial parasite, which is essential in degrading the host hemoglobin. The structure of the biological target was used to predict candidate drugs that could bind with high affi nity and selectivity to the target. The docking behaviour of target protein (2BJU) was studied in order to fi nd out the binding sites for the inhibitor on the protein molecule. The binding pocket that was selected had Phe84 and Thr341 as their active residues, depending upon which few ligand molecules were examined. Subsequently one of the ligand exhibited the best binding properties and the drug likeliness studies were carried out. Based on these studies, it could be inferred that the selected ligand could act as a potential drug candidate and thus, could also be considered for further studies.

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Molecular docking analysis of curcumin analogues as human neutrophil elastase inhibitors

Cited by 10 publications

References 31 publications

Hits-to-Lead Optimization of the Natural Compound 2,4,6-Trihydroxy-3-geranyl-acetophenone (tHGA) as a Potent LOX Inhibitor: Synthesis, Structure-Activity Relationship (SAR) Study, and Computational Assignment

In silico approaches for inhibitor designing against Plasmepsin-II of malarial parasite, Plasmodium malariae

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