Dee Bague, Graduate Student, Dowd Lab, GW Department of Chemistry

The Department of Chemistry Presents:  Dee Bague, Graduate Student, Dowd Lab, GW Department of Chemistry

The methylerythritol phosphate (MEP) pathway is responsible for isoprene synthesis in pathogens such as Mycobacterium tuberculosis (Mtb), Plasmodium falciparum (Pf), Acinetobacter baumanii (Ab), and Klebsiella pneumoniae (Kp). The process and its products are vital to microbial metabolism and survival. This pathway represents an attractive set of drug targets due to its essentiality in these pathogens but absence in humans. The second step in the MEP pathway is the conversion of 1-deoxy-D-xylulose-5-phosphate (DXP) to MEP and is catalyzed by 1-deoxy-D-xylulose-5-phosphate reductoisomerase (Dxr). Natural products fosmidomycin and FR900098 inhibit Dxr, however they lack the required lipophilicity to reach the desired target inside the cell. To further increase lipophilicity, a prodrug strategy, using acyloxy- and aryloxy-prodrug esters, were synthesized, and added to this novel series of FR900098 analogs. In addition to prodrug implementation, lipophilic modifications at various sites showed promise, resulting in increased activity against our pathogens of interest. Data from these compounds suggest that this combination of substituents is advantageous in designing a new generation of antimicrobials.

BIO

Darean Bague received her B.S. in chemistry from Schreiner University in 2016, where she worked under Dr. Danette Vines synthesizing anticancer drug analogs and antibody-drug conjugates for breast cancer. She then attended Stephen F. Austin State University in Nacogdoches, Texas where she received her M.S. in chemistry doing research under Dr. Russell Franks focusing on novel synthesis of biodiesel from alternative renewable resources. Darean then joined the chemistry department at The George Washington University in 2018 and is working towards her PhD under the guidance of Dr. Cynthia Dowd.