Synthesis, Antimalarial Activity and Molecular Dynamics Studies of Pipecolisporin: A Novel Cyclic Hexapeptide with Potent Therapeutic Potential
Malaria, caused by <i>Plasmodium</i> species and transmitted by <i>Anopheles</i> mosquitoes, continues to pose a significant global health threat. Pipecolisporin, a cyclic hexapeptide isolated from <i>Nigrospora oryzae</i>, has emerged as a promising antimalarial...
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2025-01-01
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| author | Nety Kurniaty Taufik Muhammad Fakih Rani Maharani Unang Supratman Ace Tatang Hidayat Nurhidanatasha Abu Bakar Xiaoshuang Wei |
| author_facet | Nety Kurniaty Taufik Muhammad Fakih Rani Maharani Unang Supratman Ace Tatang Hidayat Nurhidanatasha Abu Bakar Xiaoshuang Wei |
| author_sort | Nety Kurniaty |
| collection | DOAJ |
| description | Malaria, caused by <i>Plasmodium</i> species and transmitted by <i>Anopheles</i> mosquitoes, continues to pose a significant global health threat. Pipecolisporin, a cyclic hexapeptide isolated from <i>Nigrospora oryzae</i>, has emerged as a promising antimalarial candidate due to its potent biological activity and stability. This study explores the synthesis, antimalarial activity, and computational studies of pipecolisporin, aiming to better understand its therapeutic potential. The peptide was successfully synthesized using Fmoc-based solid-phase peptide synthesis (SPPS) followed by cyclization in solution. The purified compound was characterized using HPLC and mass spectrometry, confirming a molecular ion peak at <i>m</i>/<i>z</i> [M + H]<sup>+</sup> 692.4131, which matched the calculated mass. Structural verification through <sup>1</sup>H- and <sup>13</sup>C-NMR demonstrated strong alignment with the natural product. Pipecolisporin exhibited significant antimalarial activity with an IC<sub>50</sub> of 26.0 ± 8.49 nM, highlighting its efficacy. In addition to the experimental synthesis, computational studies were conducted to analyze the interaction of pipecolisporin with key malaria-related enzymes, such as dihydrofolate reductase, plasmepsin V, and lactate dehydrogenase. These combined experimental and computational insights into pipecolisporin emphasize the importance of hydrophobic interactions, particularly in membrane penetration and receptor binding, for its antimalarial efficacy. Pipecolisporin represents a promising lead for future antimalarial drug development, with its efficacy, stability, and binding characteristics laying a solid foundation for ongoing research. |
| format | Article |
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| institution | Kabale University |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj-art-efcd0d753b68409db1e355cdae8110fd2025-01-24T13:43:30ZengMDPI AGMolecules1420-30492025-01-0130230410.3390/molecules30020304Synthesis, Antimalarial Activity and Molecular Dynamics Studies of Pipecolisporin: A Novel Cyclic Hexapeptide with Potent Therapeutic PotentialNety Kurniaty0Taufik Muhammad Fakih1Rani Maharani2Unang Supratman3Ace Tatang Hidayat4Nurhidanatasha Abu Bakar5Xiaoshuang Wei6Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Islam Bandung, Jl. Ranggagading, Bandung 40116, IndonesiaDepartment of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Islam Bandung, Jl. Ranggagading, Bandung 40116, IndonesiaDepartment of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung Sumedang KM 21, Sumedang 45363, IndonesiaDepartment of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung Sumedang KM 21, Sumedang 45363, IndonesiaDepartment of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung Sumedang KM 21, Sumedang 45363, IndonesiaSchool of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, MalaysiaSchool of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, MalaysiaMalaria, caused by <i>Plasmodium</i> species and transmitted by <i>Anopheles</i> mosquitoes, continues to pose a significant global health threat. Pipecolisporin, a cyclic hexapeptide isolated from <i>Nigrospora oryzae</i>, has emerged as a promising antimalarial candidate due to its potent biological activity and stability. This study explores the synthesis, antimalarial activity, and computational studies of pipecolisporin, aiming to better understand its therapeutic potential. The peptide was successfully synthesized using Fmoc-based solid-phase peptide synthesis (SPPS) followed by cyclization in solution. The purified compound was characterized using HPLC and mass spectrometry, confirming a molecular ion peak at <i>m</i>/<i>z</i> [M + H]<sup>+</sup> 692.4131, which matched the calculated mass. Structural verification through <sup>1</sup>H- and <sup>13</sup>C-NMR demonstrated strong alignment with the natural product. Pipecolisporin exhibited significant antimalarial activity with an IC<sub>50</sub> of 26.0 ± 8.49 nM, highlighting its efficacy. In addition to the experimental synthesis, computational studies were conducted to analyze the interaction of pipecolisporin with key malaria-related enzymes, such as dihydrofolate reductase, plasmepsin V, and lactate dehydrogenase. These combined experimental and computational insights into pipecolisporin emphasize the importance of hydrophobic interactions, particularly in membrane penetration and receptor binding, for its antimalarial efficacy. Pipecolisporin represents a promising lead for future antimalarial drug development, with its efficacy, stability, and binding characteristics laying a solid foundation for ongoing research.https://www.mdpi.com/1420-3049/30/2/304pipecolisporincyclic hexapeptidesolid-phase peptide synthesis (SPPS)antimalarial candidatescomputational studies |
| spellingShingle | Nety Kurniaty Taufik Muhammad Fakih Rani Maharani Unang Supratman Ace Tatang Hidayat Nurhidanatasha Abu Bakar Xiaoshuang Wei Synthesis, Antimalarial Activity and Molecular Dynamics Studies of Pipecolisporin: A Novel Cyclic Hexapeptide with Potent Therapeutic Potential Molecules pipecolisporin cyclic hexapeptide solid-phase peptide synthesis (SPPS) antimalarial candidates computational studies |
| title | Synthesis, Antimalarial Activity and Molecular Dynamics Studies of Pipecolisporin: A Novel Cyclic Hexapeptide with Potent Therapeutic Potential |
| title_full | Synthesis, Antimalarial Activity and Molecular Dynamics Studies of Pipecolisporin: A Novel Cyclic Hexapeptide with Potent Therapeutic Potential |
| title_fullStr | Synthesis, Antimalarial Activity and Molecular Dynamics Studies of Pipecolisporin: A Novel Cyclic Hexapeptide with Potent Therapeutic Potential |
| title_full_unstemmed | Synthesis, Antimalarial Activity and Molecular Dynamics Studies of Pipecolisporin: A Novel Cyclic Hexapeptide with Potent Therapeutic Potential |
| title_short | Synthesis, Antimalarial Activity and Molecular Dynamics Studies of Pipecolisporin: A Novel Cyclic Hexapeptide with Potent Therapeutic Potential |
| title_sort | synthesis antimalarial activity and molecular dynamics studies of pipecolisporin a novel cyclic hexapeptide with potent therapeutic potential |
| topic | pipecolisporin cyclic hexapeptide solid-phase peptide synthesis (SPPS) antimalarial candidates computational studies |
| url | https://www.mdpi.com/1420-3049/30/2/304 |
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