Date of Award

Spring 4-26-2023

Document Type

Honors Project

Degree Name

Bachelor of Science

Department

Biological Sciences

Department Chair or Program Director

Lewis, Lynn

First Advisor

Lewis, Lynn

Second Advisor

Oldham, Davis

Major or Concentration

Biology

Abstract

Tuberculosis is a disease that affects the lungs caused by Mycobacterium tuberculosis (M. tuberculosis). Although drug treatment options exist, increased rates of antibiotic resistant strains have become more prevalent in recent years, driving a need for new treatment approaches. KasA, a β-ketoacyl synthase, has been found to synthesize parts of the cell wall and been identified as an attractive drug target. Previous medicinal chemistry research has been completed to synthesize six effective competitive inhibitors of KasA that would potentially block the enzyme from binding the substrate, preventing elongation of the backbone and creation of the mycolic fatty acids that form the mycobacterial cell wall, ultimately killing the bacterium. With the sulfonamide and amine derivatives fully synthesized, theses were tested by means of the microdilution broth panel method using 96-well and 24-well titration plates, as well as through SPOTi assays to determine their effectiveness as potential drug candidates. Due to M. tuberculosis being highly contagious and infectious upon contact, the surrogate model Mycobacterium aurum (M. aurum) was used since it has the same target enzyme as in M. tuberculosis. Based on the high strength of the ligand-receptor binding energy values obtained from AutoDock Tools, a molecular binding simulation software, it was concluded that the six derivatives were suitable candidates for growth inhibition. Despite complications with the microdilution broth panel with the 96-well and 24-well titration plates, there is partial evidence through the SPOTi assay to support that the N-1-methyl-6-indazolyl benzene sulfonamide derivative potentially reduces mycobacterial growth on the plates containing M. aurum.

Download

Share

COinS