Design,Synthesis, and Biological Evaluation of Peptidomimetic N‐Substituted Cbz‐4‐Hyp‐Hpa‐Amides as Novel Inhibitors of Plasmodium falciparum |
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| Authors: | Valeriy A Bacherikov Amar G Chittiboyina Mitchell A Avery |
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| Affiliation: | 1. Department of Medicinal Chemistry and Biology, Odessa Medical Institute, International Humanitarian University, Odessa, Ukraine;2. National Center for Natural Products Research, University of Mississippi, Oxford, MS, USA;3. Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, Oxford, MS, USA |
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| Abstract: | A new series of peptidomimetic N‐substituted Cbz‐4‐Hyp‐Hpa‐amides were designed, synthesized, and evaluated for inhibition of the Plasmodium falciparum. Substituents on the N‐atom of the amide group were selected alkyl‐, allyl‐, aryl‐, 2‐hydroxyethyl‐, 2‐cyanoethyl‐, cyanomethyl‐, 2‐hydroxyethyl‐, 2,2‐diethoxyethyl‐, or 2‐ethoxy‐2‐oxoethylamino groups, and about of 40 new compounds were synthesized and evaluated for antiplasmodial activity in vitro. Antimalarial activity has been investigated as for the final peptide mimetics, and their immediate predecessors, carrying TBDMS or TBDPS protecting groups on 4‐hydroxyproline residue and 18 derivatives exhibited toxicity against P. falciparum. Of these agents, compound 23e was shown to have potent antimalarial activity with IC50 528 ng/ml. |
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| Keywords: | Antimalarial activities Peptidomimetics Falcipain Drug design Synthesis |
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