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.
References
Jul 1, 1991·Applied and Environmental Microbiology·H Babich, E Borenfreund
Nov 1, 1991·The Journal of Clinical Investigation·P J RosenthalD Rasnick
Mar 1, 1993·The Journal of Clinical Investigation·P J RosenthalR E Smith
Jul 1, 1996·Antimicrobial Agents and Chemotherapy·P J RosenthalD Rasnick
Nov 14, 1997·Journal of Medicinal Chemistry·M CalasH Vial
Jun 3, 1999·Bioorganic & Medicinal Chemistry·J E OlsonP J Rosenthal
Jan 25, 2002·Journal of Medicinal Chemistry·Lily HuangJonathan A Ellman
Feb 19, 2002·Molecular and Biochemical Parasitology·M Sajid, J H McKerrow
Jul 23, 2002·Current Pharmaceutical Design·Philip J RosenthalBhaskar R Shenai
Dec 25, 2002·Antimicrobial Agents and Chemotherapy·Bhaskar R ShenaiPhilip J Rosenthal
Feb 20, 2003·Protein Science : a Publication of the Protein Society·Yogesh A SabnisMitchell A Avery
Jul 23, 2003·Current Medicinal Chemistry·Kelly Chibale, Chitalu C Musonda
Nov 26, 2003·Antimicrobial Agents and Chemotherapy·Belinda J LeePhilip J Rosenthal
Apr 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·Puran S Sijwali, Philip J Rosenthal
Dec 14, 2004·Journal of Medicinal Chemistry·Prashant V DesaiMitchell Avery
Mar 3, 2006·Journal of Medicinal Chemistry·Prashant V DesaiMitchell Avery
Apr 26, 2008·PLoS Pathogens·Dewal JaniDharmendar Rathore
Jun 17, 2008·Bioorganic & Medicinal Chemistry Letters·Edite VerissimoPaul M O'Neill
Mar 20, 2009·Journal of Medicinal Chemistry·Roberta EttariMaria Zappalà
Sep 1, 2009·Journal of Medicinal Chemistry·Uwe MachonCarsten Schmuck
Feb 6, 2010·Journal of Medicinal Chemistry·Alexander BreuningTanja Schirmeister
Apr 8, 2010·Current Computer-aided Drug Design·Falgun ShahMitchell Avery
Mar 25, 2011·Journal of Chemical Information and Modeling·Falgun ShahMitchell A Avery
Jun 11, 2011·Advances in Experimental Medicine and Biology·Philip J Rosenthal
Oct 2, 2012·Journal of Parasitic Diseases : Official Organ of the Indian Society for Parasitology·Kailash C Pandey
Mar 9, 2013·Proceedings of the National Academy of Sciences of the United States of America·Monika ChughPawan Malhotra
Feb 11, 2014·Bioorganic & Medicinal Chemistry Letters·David J WeldonMitchell A Avery
Jun 20, 2014·ACS Medicinal Chemistry Letters·María J ChaparroFélix Calderón
Dec 30, 2014·Combinatorial Chemistry & High Throughput Screening·Jahan B GhasemiZahra Heidari
Mar 17, 2016·Advances in Nutrition·Shelley McGuire