Kenneth Heidel, Graduate Student, Dowd Lab, GW Department of Chemistry

The Department of Chemistry Presents, via Online Zoom Presentation:  Kenneth Heidel, Graduate Student, GW Department of Chemistry, Dowd Lab

Please note that this presentation begins at 3:30 PM .  Thank you.

As infectious microorganisms continually develop resistance to current drug therapies, it is essential to develop next-generation drugs to combat these threats. Plasmodium falciparum, the causative agent of a malarial infection, is of particular interest, as hundreds of millions of new infections are recorded each year. Combined with a slowing decline in mortality rate, a novel mechanism of action through which to combat the parasite is urgently needed. Inhibition of isoprene biosynthesis through the methylerythritol 4-phosphate (MEP) pathway is effective in hindering the spread and growth of these infectious agents. This is accomplished by inhibition of the enzyme 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR), an enzyme not found in humans. Natural products fosmidomycin and FR900098 were shown to have potent activity against Plasmodium falciparum, but with unfavorable pharmacokinetics.

While fosmidomycin itself failed clinical trials as an antimalarial treatment, derivatives of fosmidomycin have been increasingly studied in recent years. The structure of fosmidomycin has been changed in four key positions: (1) protection of the phosphonic acid, (2) altering the 3-carbon backbone, (3) changing the N-acyl substituent, and (4) protection of the N-hydroxyl group as N-ethers. While each strategy gives insight into the structure-activity relationship (SAR) of fosmidomycin derivatives, I have primarily focused on protection of the acid and modification of the N-acyl substituent, while retaining α, β,-unsaturation that has previously demonstrated a marked increase in activity. Various prodrugs have been synthesized in hopes of retaining activity, but increasing stability relative to previously reported α, β-unsaturated phosphonodiesters. Further, a series of N-acyl analogs were synthesized to explore the SARs of the acyl moiety. This presentation will outline the design, synthesis, and biological evaluation of these series of compounds in effort to develop a novel, next-generation antimalarial medication.

BIO: After receiving his bachelor's degree in chemistry from Kalamazoo College in 2013, Kenny moved back to the DMV to begin a post-baccalaureate fellowship at the Walter Reed Army Institute of Research (WRAIR), where he worked to synthesize next-generation antimalarial compounds. Initially wanting to pursue a combined PhD/MS in analytical/forensic chemistry, he quickly changed gears and decided to continue on with a focus in drug development through organic synthesis. With an interest in antimalarial medications and living in DC, Kenny began studying at GW in the fall of 2015 under the watchful eye of Dr. Cynthia Dowd, continuing to design and synthesize novel, next-generation antimalarial medications.

Click here to Link to the Dowd Lab

There will be an online Zoom link posted the week of the seminar