Diverted total synthesis of falcitidin acyl tetrapeptides as new antimalarial leads |
| |
| Authors: | Santosh R Kotturi Brinda Somanadhan Jun-Hong Ch’ng Kevin S-W Tan Mark S Butler Martin J Lear |
| |
| Institution: | 1. Department of Chemistry and Medicinal Chemistry Program, 3 Science Drive 3, National University of Singapore, Singapore 117543, Singapore†;2. MerLion Pharmaceuticals, 41 Science Park Road, #04-03B The Gemini, Singapore Science Park II, Singapore 117610, Singapore†;3. Takeda Vaccines Pte Ltd, #04-10 Capricorn, 1 Science Park Road, Singapore Science Park II, Singapore 117528, Singapore;4. Department of Microbiology, Yong Loo Lin School of Medicine, 5 Science Drive 2, Singapore 11759, Singapore;5. Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, University of Queensland, St Lucia 4072, Queensland, Australia;6. Department of Chemistry, Graduate School of Science, Tohoku University, Aza Aramaki, Aoba-ku, Sendai 980-8578, Japan |
| |
| Abstract: | We report not only the convergent total synthesis of falcitidin, a natural inhibitor of falcipain-2 from myxobacterium Chitinophaga, but also its diversification into a new antimalarial class of N-acyl tetrapeptides (Acyl-His-Ile-Val-Pro-NH2). Despite the lack of whole-cell activity of falcitidin itself, our study led to the identification of a trifluoromethyl (CF3) analogue displaying sub-micromolar IC50 activity against Plasmodium falciparum 3D7 in a standard blood-cell assay, but only when N-tritylated on its histidine (imidazole) residue. |
| |
| Keywords: | Falcitidin Tetrapeptide Trifluoromethyl Natural products Antimalarial agents |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
