Cynthia S. Dowd

Professor Cynthia Dowd
Office:
SEH 4810
Address:
Science & Engineering Hall (SEH)
800 22nd St. NW
Washington, District Of Columbia 20052
United States
Phone:
202-994-8405
Email:
[email protected]
Website:
The Dowd Lab

Areas of Expertise

Organic Synthesis, Medicinal Chemistry, Antibiotic and Antiviral Drug Discovery, and Structure-Guided Ligand Design 

The development of resistance to current antibiotic therapies and the use of microorganisms in biological warfare have shown the weaknesses in our arsenal of antibiotic and antiviral drugs. Now, more than ever, the need for novel therapies exists. A major limitation in the development of novel anti-infectives is the identification of an appropriate biochemical target. Our research program focuses on the development of inhibitors for specific targets implicated in the survival of certain human pathogens. We are focused on Mycobacterium tuberculosis, causing TB, Plasmodium falciparum, the major organism causing malaria, and the ESKAPE pathogens. We focus on vulnerabilities in microorganism metabolism that might be targeted by small molecule therapeutic agents. Our work uses structure-guided ligand design, organic synthesis, and biological evaluation to examine these molecules and validate the biochemical target.

 

Current Research

Cynthia Dowd is currently engaged in several interdisciplinary projects related to antibiotic drug discovery and structure-based design. She enjoys collaboration with scientists in a variety of fields from several institutions and backgrounds. Students in her lab gain hands-on experience in molecular modeling, design, synthesis, and biochemical evaluation. Knowledge of diverse tools and thinking prepares them well for a future in science. 

Education

BA, University of Virginia, 1993 

PhD, Virginia Commonwealth University, 1999 

Publications

 

  • Heidel, K.M.; Dowd, C.S.* Phosphonate prodrugs: an overview and recent advances, Future Medicinal Chemistry, 2019, 11(13), 1625-1643. PMID: 31469328
  • Wang, X.; Edwards, R.L.; Ball, Hl; Johnson, C.; Haymond, A.; Girma, M.; Manikkam, M.; Brothers, R.C.; McKay, K.T.; Arnett, S.D.; Osbourn, D.M.; Alvarez, S.; Boshoff, H.I.; Meyers, M.J.; Couch, R.D.; Odom John, A.R.; Dowd, C.S.* MEPicides: α,β-Unsaturated Fosmidomycin Analogs as DXR inhibitors against Malaria, J. Med. Chem.201861(19),8847–8858. PMID: 30192536
  • Wang, X.; Dowd, C.S.* The MEP pathway: Promising drug targets in the fight against tuberculosis, ACS Infectious Diseases, 2018, 4(3), 278-290. PMID: 29390176
  • Haymond, A.; Dowdy, T.; Johny, C.; Johnson, C.; Ball, H.; Dailey, A.; Schweibenz, B.; Villarroel, K.; Young, R.; Mantooth, C.J.; Patel, T.; Bases, J.; Dowd, C.S.; Couch, R.D. A High-Throughput Screening Campaign to Identify Inhibitors of DXP Reductoisomerase (IspC) and MEP Cytidylyltransferase (IspD), Anal. Biochem., 2018, 542, 63-75. PMID: 29180070
  • Wang, X.; Ahn, Y.M.; Lentscher, A.G.; Lister, J.S.; Brothers, R.C.; Kneen, M.M.; Boshoff, H.I.; Gerratana, B.; Dowd, C.S.* Design, synthesis, and evaluation of nicotinamide adenine dinucleotide (NAD+) synthetase inhibitors as potential antitubercular agents, Bioorg. Med. Chem. Lett. 2017, 27(18), 4426-4430. PMID: 28827112
  • Edwards, R.L.; Brothers, R.C.; Wang, X.; Maron, M.I.; Ziniel, P.D.; Tsang, P.S.; Kraft, T.E.; Hruz, T.W.; Williamson, K.C.; Dowd, C.S.; Odom John, A.R. MEPicides: potent antimalarial prodrugs targeting isoprenoid biosynthesis, Sci Reports, 2017 Aug 21;7(1):8400. PMID: 28827774
  • San Jose; G.; Jackson, E.R.; Haymond, A.; Johny, C.; Edwards, R.; Wang, X.; Brothers, R.C.; Edelstein, E.; Odom, A.; Boshoff, H.I.; Couch, R.D.; Dowd, C.S.* Structure-Activity Relationships of the MEPicides: N-Acyl and O-linked Analogs of FR900098 as Inhibitors of Dxr from Mycobacterium tuberculosis and Yersinia pestis, ACS Infectious Diseases, 2016, 2(12), 923-935. PMID: 27676224
  • Sooriyaarachchi, S.; Chofor, R.; Risseeuw, M.D.P.; Bergfors, T.; Pouyez, J.; Dowd, C.S.; Maes, L.; Wouters, J.; Jones, T.A.; Van Calenbergh, S.; Mowbray, S.L.  Targeting an aromatic hotspot in Plasmodium falciparum 1-deoxy-D-xylulose 5-phosphate reductoisomerase withb-arylpropyl-analogues of fosmidomycin, ChemMedChem, 2016, 11(18), 2024-2036. PMID: 27487410
  • Chofor, R.; Sooriyaarachchi, S.; Risseeuw, M.; Bergfors, T.; Pouyez, J.; Johny, C.; Haymond, A.; Everaert, A.; Dowd, C.S.; Maes, L.; Coenye, T.; Alex, A.; Couch, R.; Jones, T.; Wouters, J.; Mowbray, S.; Van Calenbergh, S. Synthesis and bioactivity of β-substituted fosmidomycin analogues targeting 1-deoxy-D-xylulose-5-phosphate reductoisomerase, J. Med. Chem., 2015, 58(7), 2988-3001. PMID: 25781377
  • Haymond, A.; Johny, C.; Dowdy, T.; Schweibenz, B.; Villarroel, K.; Young, R.; San Jose, G.; Jackson, E.R.; Dowd, C.S.; Couch, R.D. Kinetic Characterization and Allosteric Inhibition of the Yersinia pestis 1-Deoxy-D-Xylulose 5-Phosphate Reductoisomerase (MEP Synthase), PLoS One, 2014, 9(8), e106243. doi: 10.1371/journal.pone.0106243. PMID: 25171339

Classes Taught

 2152 Organic Chemistry 2

 6251 Advanced Organic Chemistry

 6350 Medicinal Chemistry