Computational Design of Thioxanthone Derivatives as Potential Antimalarial Agents through <i>Plasmodium falciparum</i> Protein Inhibition
Plasmodium falciparum (P. falciparum) is the most fatal among the other Plasmodium parasites that infect humans with the malaria disease. Currently, the resistance of P. falciparum against some antifolate drugs has become a severe problem. On the other hand, xanthone and thioxanthone derivatives hav...
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| Format: | Article |
| Language: | English |
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Department of Chemistry, Universitas Gadjah Mada
2021-12-01
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| Series: | Indonesian Journal of Chemistry |
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| Online Access: | https://jurnal.ugm.ac.id/ijc/article/view/69448 |
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| author | Faris Hermawan Jumina Jumina Harno Dwi Pranowo Eti Nurwening Sholikhah Muthia Rahayu Iresha |
| author_facet | Faris Hermawan Jumina Jumina Harno Dwi Pranowo Eti Nurwening Sholikhah Muthia Rahayu Iresha |
| author_sort | Faris Hermawan |
| collection | DOAJ |
| description | Plasmodium falciparum (P. falciparum) is the most fatal among the other Plasmodium parasites that infect humans with the malaria disease. Currently, the resistance of P. falciparum against some antifolate drugs has become a severe problem. On the other hand, xanthone and thioxanthone derivatives have been reported to have remarkable antimalarial activity. However, molecular docking studies have not evaluated thioxanthone derivative compounds as antimalarial agents. Accordingly, this research investigated the binding pose and inhibition mechanism of several thioxanthone derivatives against P. falciparum proteins DHFR (PDB ID: 1J3K) and DHODH (PDB ID: 1TV5) through molecular docking study. The compound structures were geometrically optimized using Gaussian 09 software and docked to the receptors using AutoDock4 software. The results showed that the free binding energy of thioxanthone derivatives ranged between -6.77 to -7.50 and -8.45 to -9.55 kcal mol–1 against pfDHFR and pfDHODH, respectively, with RMSD values of less than 2 Å. Compound F (4-iodo-3,4-dihydroxy-thioxanthone) gave the most substantial free binding energy against both proteins. Furthermore, the hydrogen bond interaction of compound F was the same as the native ligands of pfDHFR and pfDHODH. These results suggested that compound F has a more robust interaction in pfDHFR and pfDHODH. Thus, it is promising to further evaluate the compound as a candidate for a new antimalarial agent. |
| first_indexed | 2024-12-13T01:17:17Z |
| format | Article |
| id | doaj.art-ce4996819721495a9a4dbc4ab4b44059 |
| institution | Directory Open Access Journal |
| issn | 1411-9420 2460-1578 |
| language | English |
| last_indexed | 2024-12-13T01:17:17Z |
| publishDate | 2021-12-01 |
| publisher | Department of Chemistry, Universitas Gadjah Mada |
| record_format | Article |
| series | Indonesian Journal of Chemistry |
| spelling | doaj.art-ce4996819721495a9a4dbc4ab4b440592022-12-22T00:04:19ZengDepartment of Chemistry, Universitas Gadjah MadaIndonesian Journal of Chemistry1411-94202460-15782021-12-0122126327110.22146/ijc.6944831161Computational Design of Thioxanthone Derivatives as Potential Antimalarial Agents through <i>Plasmodium falciparum</i> Protein InhibitionFaris Hermawan0Jumina Jumina1Harno Dwi Pranowo2Eti Nurwening Sholikhah3Muthia Rahayu Iresha4Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia Austrian-Indonesian Centre (AIC) for Computational Chemistry, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, IndonesiaDepartment of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, IndonesiaDepartment of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia Austrian-Indonesian Centre (AIC) for Computational Chemistry, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, IndonesiaDepartment of Pharmacology and Therapeutics, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, IndonesiaDepartment of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia Austrian-Indonesian Centre (AIC) for Computational Chemistry, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, IndonesiaPlasmodium falciparum (P. falciparum) is the most fatal among the other Plasmodium parasites that infect humans with the malaria disease. Currently, the resistance of P. falciparum against some antifolate drugs has become a severe problem. On the other hand, xanthone and thioxanthone derivatives have been reported to have remarkable antimalarial activity. However, molecular docking studies have not evaluated thioxanthone derivative compounds as antimalarial agents. Accordingly, this research investigated the binding pose and inhibition mechanism of several thioxanthone derivatives against P. falciparum proteins DHFR (PDB ID: 1J3K) and DHODH (PDB ID: 1TV5) through molecular docking study. The compound structures were geometrically optimized using Gaussian 09 software and docked to the receptors using AutoDock4 software. The results showed that the free binding energy of thioxanthone derivatives ranged between -6.77 to -7.50 and -8.45 to -9.55 kcal mol–1 against pfDHFR and pfDHODH, respectively, with RMSD values of less than 2 Å. Compound F (4-iodo-3,4-dihydroxy-thioxanthone) gave the most substantial free binding energy against both proteins. Furthermore, the hydrogen bond interaction of compound F was the same as the native ligands of pfDHFR and pfDHODH. These results suggested that compound F has a more robust interaction in pfDHFR and pfDHODH. Thus, it is promising to further evaluate the compound as a candidate for a new antimalarial agent.https://jurnal.ugm.ac.id/ijc/article/view/69448antimalarialthioxanthonepfdhfrpfdhodhmolecular docking |
| spellingShingle | Faris Hermawan Jumina Jumina Harno Dwi Pranowo Eti Nurwening Sholikhah Muthia Rahayu Iresha Computational Design of Thioxanthone Derivatives as Potential Antimalarial Agents through <i>Plasmodium falciparum</i> Protein Inhibition Indonesian Journal of Chemistry antimalarial thioxanthone pfdhfr pfdhodh molecular docking |
| title | Computational Design of Thioxanthone Derivatives as Potential Antimalarial Agents through <i>Plasmodium falciparum</i> Protein Inhibition |
| title_full | Computational Design of Thioxanthone Derivatives as Potential Antimalarial Agents through <i>Plasmodium falciparum</i> Protein Inhibition |
| title_fullStr | Computational Design of Thioxanthone Derivatives as Potential Antimalarial Agents through <i>Plasmodium falciparum</i> Protein Inhibition |
| title_full_unstemmed | Computational Design of Thioxanthone Derivatives as Potential Antimalarial Agents through <i>Plasmodium falciparum</i> Protein Inhibition |
| title_short | Computational Design of Thioxanthone Derivatives as Potential Antimalarial Agents through <i>Plasmodium falciparum</i> Protein Inhibition |
| title_sort | computational design of thioxanthone derivatives as potential antimalarial agents through i plasmodium falciparum i protein inhibition |
| topic | antimalarial thioxanthone pfdhfr pfdhodh molecular docking |
| url | https://jurnal.ugm.ac.id/ijc/article/view/69448 |
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