Potential of polyether ionophore compounds as antimalarials through inhibition on Plasmodium falciparum glutathione S-transferase by molecular docking studies
Context: Malaria is still a serious global health problem due to the development of drug resistance. It is necessary to find new drugs with renewable mechanisms that are effective in killing parasites. Our previous research has analyzed more than one compound of polyether ionophore group in ethyl ac...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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GarVal Editorial Ltda.
2022-11-01
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| Series: | Journal of Pharmacy & Pharmacognosy Research |
| Subjects: | |
| Online Access: | https://jppres.com/jppres/pdf/vol10/jppres22.1478_10.6.1139.pdf |
| _version_ | 1811296499523387392 |
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| author | Alfian Wika Cahyono Icha Farihah Deniyati Faratisha Nabila Erina Erwan Rivo Yudhinata Brian Nugraha Ajeng Maharani Putri Loeki Enggar Fitri |
| author_facet | Alfian Wika Cahyono Icha Farihah Deniyati Faratisha Nabila Erina Erwan Rivo Yudhinata Brian Nugraha Ajeng Maharani Putri Loeki Enggar Fitri |
| author_sort | Alfian Wika Cahyono |
| collection | DOAJ |
| description | Context: Malaria is still a serious global health problem due to the development of drug resistance. It is necessary to find new drugs with renewable mechanisms that are effective in killing parasites. Our previous research has analyzed more than one compound of polyether ionophore group in ethyl acetate Streptomyces hygroscopicus subsp. hygroscopicus extract. Polyether ionophore is known to have a similar mechanism of action to chloroquine which is potent in inhibiting Plasmodium falciparum glutathione S-transferase (PfGST).
Aims: To evaluate the potential effect of polyether ionophore toward PfGST as a target protein through molecular docking.
Methods: PfGST was obtained from Protein Data Bank. Test ligands (polyether ionophore) and control ligands (chloroquine) were obtained from PubChem. Pharmacokinetic analysis was done using SwissADME, molecular docking using PyRx 0.9, visualization using LigPlot and PyMOL, and molecular dynamics using YASARA for the best ligand activity.
Results: Lenoremycin had the highest binding affinity to PfGST (-8.53 kcal/mol) among other polyether ionophores, and nigericin had the best residue bonding with hydrophobic and hydrogen with a binding affinity of -8.25 kcal/mol compared to chloroquine complex in molecular docking and molecular dynamic simulation.
Conclusions: Polyether ionophore could serve as an antimalarial agent better than chloroquine, with nigericin as the best compound candidate in inhibiting PfGST compared to other polyether ionophores. |
| first_indexed | 2024-04-13T05:49:27Z |
| format | Article |
| id | doaj.art-58ea17047ed54aa1a15d1b58bd029a72 |
| institution | Directory Open Access Journal |
| issn | 0719-4250 |
| language | English |
| last_indexed | 2024-04-13T05:49:27Z |
| publishDate | 2022-11-01 |
| publisher | GarVal Editorial Ltda. |
| record_format | Article |
| series | Journal of Pharmacy & Pharmacognosy Research |
| spelling | doaj.art-58ea17047ed54aa1a15d1b58bd029a722022-12-22T02:59:50ZengGarVal Editorial Ltda.Journal of Pharmacy & Pharmacognosy Research0719-42502022-11-0110611391148https://doi.org/10.56499/jppres22.1478_10.6.1139Potential of polyether ionophore compounds as antimalarials through inhibition on Plasmodium falciparum glutathione S-transferase by molecular docking studiesAlfian Wika Cahyono0Icha Farihah Deniyati Faratisha1Nabila Erina Erwan2Rivo Yudhinata Brian Nugraha3Ajeng Maharani Putri4Loeki Enggar Fitri5Malaria Research Group, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, 65145, Indonesia. Doctoral Program in Medical Science, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, 65145, Indonesia.Malaria Research Group, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, 65145, Indonesia.Malaria Research Group, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, 65145, Indonesia. Master Program in Biomedical Science, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, 65145, Indonesia.Malaria Research Group, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, 65145, Indonesia. Department of Parasitology, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, 65145, Indonesia.Malaria Research Group, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, 65145, Indonesia. Master Program in Biomedical Science, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, 65145, Indonesia.Malaria Research Group, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, 65145, Indonesia. Department of Parasitology, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, 65145, Indonesia.Context: Malaria is still a serious global health problem due to the development of drug resistance. It is necessary to find new drugs with renewable mechanisms that are effective in killing parasites. Our previous research has analyzed more than one compound of polyether ionophore group in ethyl acetate Streptomyces hygroscopicus subsp. hygroscopicus extract. Polyether ionophore is known to have a similar mechanism of action to chloroquine which is potent in inhibiting Plasmodium falciparum glutathione S-transferase (PfGST). Aims: To evaluate the potential effect of polyether ionophore toward PfGST as a target protein through molecular docking. Methods: PfGST was obtained from Protein Data Bank. Test ligands (polyether ionophore) and control ligands (chloroquine) were obtained from PubChem. Pharmacokinetic analysis was done using SwissADME, molecular docking using PyRx 0.9, visualization using LigPlot and PyMOL, and molecular dynamics using YASARA for the best ligand activity. Results: Lenoremycin had the highest binding affinity to PfGST (-8.53 kcal/mol) among other polyether ionophores, and nigericin had the best residue bonding with hydrophobic and hydrogen with a binding affinity of -8.25 kcal/mol compared to chloroquine complex in molecular docking and molecular dynamic simulation. Conclusions: Polyether ionophore could serve as an antimalarial agent better than chloroquine, with nigericin as the best compound candidate in inhibiting PfGST compared to other polyether ionophores.https://jppres.com/jppres/pdf/vol10/jppres22.1478_10.6.1139.pdfmalariamolecular dockingpfgstpolyether ionophorestreptomyces hygroscopicus |
| spellingShingle | Alfian Wika Cahyono Icha Farihah Deniyati Faratisha Nabila Erina Erwan Rivo Yudhinata Brian Nugraha Ajeng Maharani Putri Loeki Enggar Fitri Potential of polyether ionophore compounds as antimalarials through inhibition on Plasmodium falciparum glutathione S-transferase by molecular docking studies Journal of Pharmacy & Pharmacognosy Research malaria molecular docking pfgst polyether ionophore streptomyces hygroscopicus |
| title | Potential of polyether ionophore compounds as antimalarials through inhibition on Plasmodium falciparum glutathione S-transferase by molecular docking studies |
| title_full | Potential of polyether ionophore compounds as antimalarials through inhibition on Plasmodium falciparum glutathione S-transferase by molecular docking studies |
| title_fullStr | Potential of polyether ionophore compounds as antimalarials through inhibition on Plasmodium falciparum glutathione S-transferase by molecular docking studies |
| title_full_unstemmed | Potential of polyether ionophore compounds as antimalarials through inhibition on Plasmodium falciparum glutathione S-transferase by molecular docking studies |
| title_short | Potential of polyether ionophore compounds as antimalarials through inhibition on Plasmodium falciparum glutathione S-transferase by molecular docking studies |
| title_sort | potential of polyether ionophore compounds as antimalarials through inhibition on plasmodium falciparum glutathione s transferase by molecular docking studies |
| topic | malaria molecular docking pfgst polyether ionophore streptomyces hygroscopicus |
| url | https://jppres.com/jppres/pdf/vol10/jppres22.1478_10.6.1139.pdf |
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