Kurniaty Nety, Fakih Taufik Muhammad, Maharani Rani, Supratman Unang, Hidayat Ace Tatang, Bakar Nurhidanatasha Abu, Wei Xiaoshuang
Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Islam Bandung, Jl. Ranggagading, Bandung 40116, Indonesia.
Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung Sumedang KM 21, Sumedang 45363, Indonesia.
Molecules. 2025 Jan 14;30(2):304. doi: 10.3390/molecules30020304.
Malaria, caused by species and transmitted by mosquitoes, continues to pose a significant global health threat. Pipecolisporin, a cyclic hexapeptide isolated from , 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 + H] 692.4131, which matched the calculated mass. Structural verification through H- and C-NMR demonstrated strong alignment with the natural product. Pipecolisporin exhibited significant antimalarial activity with an IC 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.
由疟原虫物种引起并通过蚊子传播的疟疾，仍然对全球健康构成重大威胁。从[具体来源未提及]中分离出的环六肽哌可利孢菌素，因其强大的生物活性和稳定性，已成为一种有前景的抗疟候选药物。本研究探索了哌可利孢菌素的合成、抗疟活性及计算研究，旨在更好地了解其治疗潜力。该肽通过基于Fmoc的固相肽合成（SPPS）成功合成，随后在溶液中环化。使用高效液相色谱（HPLC）和质谱对纯化后的化合物进行表征，确认其分子离子峰为/ [M + H] 692.4131，与计算质量相符。通过氢核磁共振（H-NMR）和碳核磁共振（C-NMR）进行的结构验证表明，其与天然产物高度一致。哌可利孢菌素表现出显著的抗疟活性，半数抑制浓度（IC）为26.0 ± 8.49 nM，突出了其有效性。除了实验合成外，还进行了计算研究，以分析哌可利孢菌素与关键疟疾相关酶（如二氢叶酸还原酶、疟原虫天冬氨酸蛋白酶V和乳酸脱氢酶）的相互作用。这些对哌可利孢菌素的实验和计算相结合的见解强调了疏水相互作用的重要性，特别是在膜渗透和受体结合方面，对其抗疟疗效的重要性。哌可利孢菌素代表了未来抗疟药物开发的一个有前景的先导化合物，其有效性、稳定性和结合特性为正在进行的研究奠定了坚实基础。
