Premium
A Fragmenting Hybrid Approach for Targeted Delivery of Multiple Therapeutic Agents to the Malaria Parasite
Author(s) -
Mahajan Sumit S.,
Deu Edgar,
Lauterwasser Erica M. W.,
Leyva Melissa J.,
Ellman Jonathan A.,
Bogyo Matthew,
Renslo Adam R.
Publication year - 2011
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201100002
Subject(s) - artemisinin , malaria , combinatorial chemistry , drug , plasmodium falciparum , pharmacology , drug delivery , malaria vaccine , drug resistance , chemistry , biology , immunology , microbiology and biotechnology , organic chemistry
Hybrid drugs with a twist: The coupling of iron(II)‐promoted trioxolane ring scission with a β‐elimination reaction enables the targeted delivery of multiple drug activities to the malaria parasite. A prototypical fragmenting hybrid (shown) comprises an iron(II)‐reactive 1,2,4‐trioxolane ring (red) joined via a masked retro‐Michael linker (blue) to a partner drug—in this case a protease inhibitor (green). Successful delivery of the protease inhibitor to intra‐erythrocytic Plasmodium falciparum parasites is demonstrated using a chemical–biological approach.