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Design, Synthesis, and Biological Evaluation of Peptidomimetic N ‐Substituted Cbz‐4‐Hyp‐Hpa‐Amides as Novel Inhibitors of Plasmodium falciparum
Author(s) -
Bacherikov Valeriy A.,
Chittiboyina Amar G.,
Avery Mitchell A.
Publication year - 2017
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.201700037
Subject(s) - peptidomimetic , chemistry , plasmodium falciparum , amide , aryl , stereochemistry , alkyl , residue (chemistry) , peptide , in vitro , biological activity , antimalarial agent , combinatorial chemistry , organic chemistry , biochemistry , malaria , immunology , biology
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 IC 50 528 ng/ml.