{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T13:04:01Z","timestamp":1781701441512,"version":"3.54.5"},"reference-count":55,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T00:00:00Z","timestamp":1736812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Academic Leadership Grant (ALG) research grant of Universitas Padjadjaran","award":["1528\/UN6.3.1\/PT.00\/2024"],"award-info":[{"award-number":["1528\/UN6.3.1\/PT.00\/2024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Malaria, caused by Plasmodium species and transmitted by Anopheles mosquitoes, continues to pose a significant global health threat. Pipecolisporin, a cyclic hexapeptide isolated from Nigrospora oryzae, 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 m\/z [M + H]+ 692.4131, which matched the calculated mass. Structural verification through 1H- and 13C-NMR demonstrated strong alignment with the natural product. Pipecolisporin exhibited significant antimalarial activity with an IC50 of 26.0 \u00b1 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.<\/jats:p>","DOI":"10.3390\/molecules30020304","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T06:13:07Z","timestamp":1736835187000},"page":"304","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Synthesis, Antimalarial Activity and Molecular Dynamics Studies of Pipecolisporin: A Novel Cyclic Hexapeptide with Potent Therapeutic Potential"],"prefix":"10.3390","volume":"30","author":[{"given":"Nety","family":"Kurniaty","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Islam Bandung, Jl. Ranggagading, Bandung 40116, Indonesia"},{"name":"Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung Sumedang KM 21, Sumedang 45363, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7155-4412","authenticated-orcid":false,"given":"Taufik Muhammad","family":"Fakih","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Islam Bandung, Jl. Ranggagading, Bandung 40116, Indonesia"},{"name":"Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung Sumedang KM 21, Sumedang 45363, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rani","family":"Maharani","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung Sumedang KM 21, Sumedang 45363, Indonesia"},{"name":"Laboratorium Sentral, Universitas Padjadjaran, Jl. Raya Bandung Sumedang KM 21, Sumedang 45363, Indonesia"},{"name":"Centre of Exploration and Utilization of Natural Resources and Environment Studies, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung Sumedang KM 21, Sumedang 45363, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1104-2321","authenticated-orcid":false,"given":"Unang","family":"Supratman","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung Sumedang KM 21, Sumedang 45363, Indonesia"},{"name":"Laboratorium Sentral, Universitas Padjadjaran, Jl. Raya Bandung Sumedang KM 21, Sumedang 45363, Indonesia"},{"name":"Centre of Exploration and Utilization of Natural Resources and Environment Studies, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung Sumedang KM 21, Sumedang 45363, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ace Tatang","family":"Hidayat","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung Sumedang KM 21, Sumedang 45363, Indonesia"},{"name":"Laboratorium Sentral, Universitas Padjadjaran, Jl. Raya Bandung Sumedang KM 21, Sumedang 45363, Indonesia"},{"name":"Centre of Exploration and Utilization of Natural Resources and Environment Studies, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung Sumedang KM 21, Sumedang 45363, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurhidanatasha Abu","family":"Bakar","sequence":"additional","affiliation":[{"name":"School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoshuang","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e214","DOI":"10.1016\/S2666-5247(24)00016-8","article-title":"The 2023 WHO World Malaria Report","volume":"5","author":"Venkatesan","year":"2024","journal-title":"Lancet Microbe"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"a025569","DOI":"10.1101\/cshperspect.a025569","article-title":"Malaria pathogenesis","volume":"8","author":"Milner","year":"2018","journal-title":"Cold Spring Harb. 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