Fighting Tuberculosis in an Undergraduate Laboratory: Synthesizing, Evaluating and Analyzing Inhibitors

Abstract

A drug discovery project has been successfully implemented in a first-year general, organic, and biochemistry (GOB) health science course and second-year organic undergraduate chemistry course. This project allows students to apply the fundamental principles of chemistry and biology to a problem of medical significance, practice basic laboratory skills, and understand the interdisciplinary aspect of the drug discovery platform. Students collectively synthesize a small library of antituberculosis compounds and subsequently screen them using a Kirby–Bauer disc diffusion assay for inhibitory activity against Mycobacterium smegmatis, a known safe surrogate of Mycobacterium tuberculosis, the causative agent of tuberculosis. The last unit of the project involves students using PyMOL, a free computer program, to examine a cocrystal structure of the activated inhibitor–enzyme complex, allowing students to identify the molecular interactions responsible for the binding affinity.