In silico screening of Andrographis paniculata secondary metabolites as anti-diabetes mellitus through PDE9 inhibition
Background and purpose: Andrographis paniculata (AP) has long been used as an anti-diabetic agent, but the mechanism of action and active substance responsible for the anti-diabetic effect, particularly by inhibiting phosphodiesterase-9 (PDE9), which is one of the targets of anti-diabetic medication...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2023-01-01
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| Series: | Research in Pharmaceutical Sciences |
| Subjects: | |
| Online Access: | http://www.rpsjournal.net/article.asp?issn=1735-5362;year=2023;volume=18;issue=1;spage=100;epage=111;aulast=Ischak |
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| author | Netty Ino Ischak La Aman Ode Hamsidar Hasan Akram La Kilo Aiyi Asnawi |
| author_facet | Netty Ino Ischak La Aman Ode Hamsidar Hasan Akram La Kilo Aiyi Asnawi |
| author_sort | Netty Ino Ischak |
| collection | DOAJ |
| description | Background and purpose: Andrographis paniculata (AP) has long been used as an anti-diabetic agent, but the mechanism of action and active substance responsible for the anti-diabetic effect, particularly by inhibiting phosphodiesterase-9 (PDE9), which is one of the targets of anti-diabetic medications, have not been reported. The aim of the present study was to identify a new anti-diabetes candidate from secondary metabolite compounds of AP through PDE9 inhibition.
Experimental approach: In order to prepare the chemical structures of the secondary metabolites of AP and PDE9, docking and molecular dynamics simulations were run using Discovery Studio Visualizer, AutoDockTools, AutoDock, and Gromacs, along with a few other supporting software packages.
Findings/Results: Molecular docking simulations showed that two of the 46 secondary metabolites of AP had higher free energies of binding, C00003672 (-11.35 kcal/mol) and C00041378 (-9.27 kcal/mol), than native ligand (-9.23 kcal/mol). The results of molecular dynamics showed that compound C00041378 interacted with TRY484 and PHE516, two active side residues of PDE9. ΔGMMGBSA interactions of PDE9 with C00003672, C00041378, and 49E compounds are 51.69, -56.43, and -48.13 kcal/mol, respectively, as well as ΔGMMPBSA interactions of PDE9 with C00003672, C00041378, and 49E compounds, were -12.26, -16.24, and -11.79 kcal/mol kcal/mol, respectively.
Conclusions and implications: Based on the evaluations of AP secondary metabolites using docking and molecular dynamics simulation, it is suggested that the C00041378 compound has the potential to be an antidiabetic candidate by inhibiting PDE9. |
| first_indexed | 2024-04-10T23:23:24Z |
| format | Article |
| id | doaj.art-b5b80b09bed5486fae56309dca57aff2 |
| institution | Directory Open Access Journal |
| issn | 1735-5362 1735-9414 |
| language | English |
| last_indexed | 2024-04-10T23:23:24Z |
| publishDate | 2023-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Research in Pharmaceutical Sciences |
| spelling | doaj.art-b5b80b09bed5486fae56309dca57aff22023-01-12T13:32:40ZengWolters Kluwer Medknow PublicationsResearch in Pharmaceutical Sciences1735-53621735-94142023-01-0118110011110.4103/1735-5362.363619In silico screening of Andrographis paniculata secondary metabolites as anti-diabetes mellitus through PDE9 inhibitionNetty Ino IschakLa Aman OdeHamsidar HasanAkram La KiloAiyi AsnawiBackground and purpose: Andrographis paniculata (AP) has long been used as an anti-diabetic agent, but the mechanism of action and active substance responsible for the anti-diabetic effect, particularly by inhibiting phosphodiesterase-9 (PDE9), which is one of the targets of anti-diabetic medications, have not been reported. The aim of the present study was to identify a new anti-diabetes candidate from secondary metabolite compounds of AP through PDE9 inhibition. Experimental approach: In order to prepare the chemical structures of the secondary metabolites of AP and PDE9, docking and molecular dynamics simulations were run using Discovery Studio Visualizer, AutoDockTools, AutoDock, and Gromacs, along with a few other supporting software packages. Findings/Results: Molecular docking simulations showed that two of the 46 secondary metabolites of AP had higher free energies of binding, C00003672 (-11.35 kcal/mol) and C00041378 (-9.27 kcal/mol), than native ligand (-9.23 kcal/mol). The results of molecular dynamics showed that compound C00041378 interacted with TRY484 and PHE516, two active side residues of PDE9. ΔGMMGBSA interactions of PDE9 with C00003672, C00041378, and 49E compounds are 51.69, -56.43, and -48.13 kcal/mol, respectively, as well as ΔGMMPBSA interactions of PDE9 with C00003672, C00041378, and 49E compounds, were -12.26, -16.24, and -11.79 kcal/mol kcal/mol, respectively. Conclusions and implications: Based on the evaluations of AP secondary metabolites using docking and molecular dynamics simulation, it is suggested that the C00041378 compound has the potential to be an antidiabetic candidate by inhibiting PDE9.http://www.rpsjournal.net/article.asp?issn=1735-5362;year=2023;volume=18;issue=1;spage=100;epage=111;aulast=Ischakandrographis paniculate; anti-diabetic; molecular docking; molecular dynamicspde9; secondary metabolites. |
| spellingShingle | Netty Ino Ischak La Aman Ode Hamsidar Hasan Akram La Kilo Aiyi Asnawi In silico screening of Andrographis paniculata secondary metabolites as anti-diabetes mellitus through PDE9 inhibition Research in Pharmaceutical Sciences andrographis paniculate; anti-diabetic; molecular docking; molecular dynamics pde9; secondary metabolites. |
| title | In silico screening of Andrographis paniculata secondary metabolites as anti-diabetes mellitus through PDE9 inhibition |
| title_full | In silico screening of Andrographis paniculata secondary metabolites as anti-diabetes mellitus through PDE9 inhibition |
| title_fullStr | In silico screening of Andrographis paniculata secondary metabolites as anti-diabetes mellitus through PDE9 inhibition |
| title_full_unstemmed | In silico screening of Andrographis paniculata secondary metabolites as anti-diabetes mellitus through PDE9 inhibition |
| title_short | In silico screening of Andrographis paniculata secondary metabolites as anti-diabetes mellitus through PDE9 inhibition |
| title_sort | in silico screening of andrographis paniculata secondary metabolites as anti diabetes mellitus through pde9 inhibition |
| topic | andrographis paniculate; anti-diabetic; molecular docking; molecular dynamics pde9; secondary metabolites. |
| url | http://www.rpsjournal.net/article.asp?issn=1735-5362;year=2023;volume=18;issue=1;spage=100;epage=111;aulast=Ischak |
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