Abstract
BackgroundThe high rate of mortality due to malaria and the worldwide distribution of parasite resistance to the commonly used antimalarial drugs chloroquine and pyrimethamine emphasize the urgent need for the development of new antimalarial drugs. An alternative approach to the long and uncertain process of designing and developing new compounds is to identify among the armamentarium of drugs already approved for clinical treatment of various human diseases those that may have strong antimalarial activity.MethodsProteasome inhibitor bortezomib (Velcade™: [(1R)-3-methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl) amino]propyl]amino]butyl] boronic acid), which has been approved for treatment of patients with multiple myeloma, and a second boronate analog Z-Leu-Leu-Leu-B(OH)2 (ZL3B), were tested against four different strains of P. falciparum (3D7, HB3, W2 and Dd2) that are either sensitive or have different levels of resistance to the antimalarial drugs pyrimethamine and chloroquine.ResultsBortezomib and ZL3B are equally effective against drug-sensitive and -resistant parasites and block intraerythrocytic development prior to DNA synthesis, but have no effect on parasite egress or invasion.ConclusionThe identification of bortezomib and its analog as potent antimalarial drugs will set the stage for the advancement of this class of compounds, either alone or in combination therapy, for treatment of malaria, and emphasize the need for large-scale screens to identify new antimalarials within the library of clinically approved compounds.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.