Tuberculosis and malaria are caused by the pathogens Mycobacterium tuberculosis (Mtb) and Plasmodium falciparum (Pf), respectively, and are two of the world’s deadliest infectious diseases. As such, their complicated life cycles and the emergence of resistant strains highlight the necessity for novel treatments. Many modern antibiotics primarily target metabolic enzymes. As with most microbes, Mtb andPf rely heavily on these proteins to synthesize important secondary metabolites. Deoxy-D-xylulose-5-phosphate reductoisomerase (Dxr) has been identified as an essential enzyme because of its role in isoprenoid biosynthesis. Its importance in the methyl erythritol phosphate (MEP) pathway and presence in Mtb and Pf but not in humans highlight Dxr asa key target for inhibition. The natural products fosmidomycin and FR900098 are retrohydroxamic acids that act as Dxr inhibitors but exhibit poor pharmacokinetic properties and face challenges in cell permeability. Based on these structures and prior inhibitors from our lab, we have designed and synthesized a novel series of small molecule fosmidomycin analogs with a variety of N-acyl substituents. Achieving considerable in vitro potency against Pf, we present the synthesis and early biological evaluation of these compounds as therapeutic agents for malaria and tuberculosis.<br/>

Novel small molecule design and synthesis to inhibit Dxr and combat malaria and tuberculosis

Macromolecular Chemistry: The Second Century

[Author Benefits](https://scimeetings.acs.org/?utm_source=pubs_content_marketing&utm_medium=website&utm_campaign=0320_MCF_NPI_Launch_Spring_Homepage&ref=pubs_content_marketing)

[How to use SciMeetings](https://storage.googleapis.com/dl.morressier.com/acs/SciMeetings-ACSSpring2020-HowToGuide_M3020-Final.pdf)

[Frequently Asked Questions](https://storage.googleapis.com/dl.morressier.com/acs/SciMtng_ACSNMSp2020_FAQ_M3120_Final.pdf)

ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.