Target Oriented Design and Synthesis of Novel Antitubercular Agents and Antimalarials

Tuberculosis and malaria are severe infectious diseases caused by Mycobacterium tuberculosis and Plasmodium falciparum respectively. Both pathogens utilize the MEP pathway to produce IPP and DMAPP, which are essential metabolites to synthesize isoprenoids. DXR, the second enzyme in the MEP pathway, catalyzes the first committed step. It is a promising drug target for tuberculosis and malaria due to its essentiality in these pathogens, as well as its absence in humans, cuing a lower human toxicity. The goals of this work are the target oriented design and synthesis of DXR inhibitors, which could act as novel antitubercular agents and antimalarials. Four series of compounds were designed and synthesized. Some compounds from these series showed great promise as drug candidates in the fight against tuberculosis and malaria. The synthetic and biological results of this work will be presented.

Author

• Wang, Xu

Language

• en

Keyword

• drug resistance
• DXR
• malaria
• antibiotics
• MEP pathway
• tuberculosis

Date created

• 2018

Type of Work

• Dissertation

License

• All rights reserved

Rights statement

• In Copyright

GW Unit

• Chemistry

Degree

• Ph.D.

Advisor

• Dowd, Cynthia S

Committee Member(s)

• King, Michael M.
• Freel Meyers, Caren L.
• Voutchkova-Kostal, Adelina
• Vertes, Akos

Persistent URL

•  https://scholarspace.library.gwu.edu/etd/bv73c0666