| |
| author |
Daniel Blumenthal
| | title |
Discovery of novel isoindole antibacterial compounds
| | abstract |
Antibacterial resistance continues to rise as the use of antimicrobial compounds selects
for resistant strains to survive and repopulate. By the year 2050, the leading cause of death in the
world is projected to be antimicrobial infections causing 10 million deaths per year. The drug
discovery process from start to finish averages 10 years in length and 2.6 billion dollars in
investment. New antibiotics are generally held in reserve to reduce the chance of resistance to
develop. This results in a lack of monetary incentive, which discourages large pharmaceutical
companies from investing and leaves the role of development of new antimicrobial compounds
to academic research laboratories and small biotech companies. Novel isoindole compounds
synthesized at Drew are being optimized for antibacterial potency using a five step synthesis.
The compounds are designed based on inhibition of the putative target of the isoindoles, FtsZ, a
protein critical to bacterial cytokinesis. Synthesis of a key intermediate compound 4,
1-(4-bromobenzyl)-1 -(4-chlorophenyl)-3-ethoxy-1 H-isoindole, leads to a compound that can be
reacted in 1 step to vary the amine side chain at the 3-position (R2) in order to explore the
antibacterial potency of the final product. The aminopropyl side chain resulted in the highest
potency against Staphylococcus aureus likely due to better chelation to the Ca2+ located in the
interdomain cleft of the FtsZ protein.
| | school |
The College of Liberal Arts, Drew University
| | degree |
B.S. (2022)
|
| advisor |
Dr. Vincent Gullo
|
| committee |
Dr. Christopher Fazen
Dr. Justine Fernandez
|
| full text | DBlumenthal.pdf |
| |
