Arylpyrrole derivatives as anti-malarial agents- in vivo and in silico investigations
Abstract Plasmodium falciparum, has been found to be resistant to practically every antimalarial medication now on the market. Consequently, it is imperative to develop new antimalarial agents with novel mechanistic pathway to stem the tide of P. falciparum resistance. In this study, the capacity of...
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| Format: | Article |
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Springer
2025-05-01
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| Series: | Discover Chemistry |
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| Online Access: | https://doi.org/10.1007/s44371-025-00176-1 |
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| author | Chiamaka Gift Iwegbulam Oluwatoba Emmanuel Oyeneyin Ogunyemi Oderinlo Damilola Alex Omoboyowa Niyi Adelakun Nash Oyekanmi Idowu Olaposi Omotuyi |
| author_facet | Chiamaka Gift Iwegbulam Oluwatoba Emmanuel Oyeneyin Ogunyemi Oderinlo Damilola Alex Omoboyowa Niyi Adelakun Nash Oyekanmi Idowu Olaposi Omotuyi |
| author_sort | Chiamaka Gift Iwegbulam |
| collection | DOAJ |
| description | Abstract Plasmodium falciparum, has been found to be resistant to practically every antimalarial medication now on the market. Consequently, it is imperative to develop new antimalarial agents with novel mechanistic pathway to stem the tide of P. falciparum resistance. In this study, the capacity of arylpyrrole-3-carbaldehydes, DPPC(A) to DPPC(E), to target P. falciparum protein kinase 7 was tested. The molecules were optimized using DFT/B3LYP/6-31G(d) level of theory while the pharmacokinetics properties were generated. The compounds were also screened against kinase 7 protease and compared with Pyrimethamine, a standard antimalarial drug via molecular docking technique. Molecular dynamics (MD) simulation was used to investigate the lead molecule’s stability. DPPC(E) was synthesized and in vivo study was carried out. The DFT results revealed the compounds chemical reactivity sites. Pharmacokinetics evaluation showed all the compounds had good drug-like properties and were non-toxic. Molecular docking revealed that DPPC(E) had the best protein interaction with a docking score of − 7.395 kcal/mol while pyrimethamine bound with a score of − 9.511 kcal/mol. MD simulation showed the molecule was stable in the protein core (95 ns) before its exit while pyrimethamine was stable at the binding domain for the simulation period (100 ns). The parasitemia count and percentage parasitemia suppression showed that DPPC(E) significantly (P < 0.05) reduced the parasitemia level but not total clearance from the red blood cells. These results showed DPPC(E) as an ideal candidate for the discovery of new antimalarial drugs. Therefore, it could be used as a template in developing novel antimalarial agents that targets plasmodial kinases. |
| format | Article |
| id | doaj-art-b5d626e86bcc4faba0da5b3f9b4c7e02 |
| institution | DOAJ |
| issn | 3005-1193 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Chemistry |
| spelling | doaj-art-b5d626e86bcc4faba0da5b3f9b4c7e022025-08-20T03:08:44ZengSpringerDiscover Chemistry3005-11932025-05-012112310.1007/s44371-025-00176-1Arylpyrrole derivatives as anti-malarial agents- in vivo and in silico investigationsChiamaka Gift Iwegbulam0Oluwatoba Emmanuel Oyeneyin1Ogunyemi Oderinlo2Damilola Alex Omoboyowa3Niyi Adelakun4Nash Oyekanmi5Idowu Olaposi Omotuyi6Theoretical and Computational Chemistry Unit, Department of Chemical Sciences, Adekunle Ajasin UniversityTheoretical and Computational Chemistry Unit, Department of Chemical Sciences, Adekunle Ajasin UniversityDepartment of Chemistry, School of Mineral and Physical Sciences, University of LimpopoPhyto-Medicine and Computational Biology Lab., Department of Biochemistry, Adekunle Ajasin UniversityDepartment of Cancer Biology and Genetics, the Comprehensive Cancer Center, College of Medicine, The Ohio State UniversityCentre for Genomics Research and Innovation, National Biotechnology Research and Development AgencyInstitute for Drug Research and Development, S.E. Bogoro Center, Afe Babalola University Ado-EkitiAbstract Plasmodium falciparum, has been found to be resistant to practically every antimalarial medication now on the market. Consequently, it is imperative to develop new antimalarial agents with novel mechanistic pathway to stem the tide of P. falciparum resistance. In this study, the capacity of arylpyrrole-3-carbaldehydes, DPPC(A) to DPPC(E), to target P. falciparum protein kinase 7 was tested. The molecules were optimized using DFT/B3LYP/6-31G(d) level of theory while the pharmacokinetics properties were generated. The compounds were also screened against kinase 7 protease and compared with Pyrimethamine, a standard antimalarial drug via molecular docking technique. Molecular dynamics (MD) simulation was used to investigate the lead molecule’s stability. DPPC(E) was synthesized and in vivo study was carried out. The DFT results revealed the compounds chemical reactivity sites. Pharmacokinetics evaluation showed all the compounds had good drug-like properties and were non-toxic. Molecular docking revealed that DPPC(E) had the best protein interaction with a docking score of − 7.395 kcal/mol while pyrimethamine bound with a score of − 9.511 kcal/mol. MD simulation showed the molecule was stable in the protein core (95 ns) before its exit while pyrimethamine was stable at the binding domain for the simulation period (100 ns). The parasitemia count and percentage parasitemia suppression showed that DPPC(E) significantly (P < 0.05) reduced the parasitemia level but not total clearance from the red blood cells. These results showed DPPC(E) as an ideal candidate for the discovery of new antimalarial drugs. Therefore, it could be used as a template in developing novel antimalarial agents that targets plasmodial kinases.https://doi.org/10.1007/s44371-025-00176-1ArylpyrrolesMalariaMolecular dockingMolecular dynamics simulationIn vivo |
| spellingShingle | Chiamaka Gift Iwegbulam Oluwatoba Emmanuel Oyeneyin Ogunyemi Oderinlo Damilola Alex Omoboyowa Niyi Adelakun Nash Oyekanmi Idowu Olaposi Omotuyi Arylpyrrole derivatives as anti-malarial agents- in vivo and in silico investigations Discover Chemistry Arylpyrroles Malaria Molecular docking Molecular dynamics simulation In vivo |
| title | Arylpyrrole derivatives as anti-malarial agents- in vivo and in silico investigations |
| title_full | Arylpyrrole derivatives as anti-malarial agents- in vivo and in silico investigations |
| title_fullStr | Arylpyrrole derivatives as anti-malarial agents- in vivo and in silico investigations |
| title_full_unstemmed | Arylpyrrole derivatives as anti-malarial agents- in vivo and in silico investigations |
| title_short | Arylpyrrole derivatives as anti-malarial agents- in vivo and in silico investigations |
| title_sort | arylpyrrole derivatives as anti malarial agents in vivo and in silico investigations |
| topic | Arylpyrroles Malaria Molecular docking Molecular dynamics simulation In vivo |
| url | https://doi.org/10.1007/s44371-025-00176-1 |
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