Development of macrocyclic hexapeptide wollamide B analogs as new antituberculosis agents
Natural products represent one of the most valuable sources for novel bioactive molecules and chemical diversity in drug discovery. Historically, the majority of antimicrobial agents, including TB drugs, originate from natural products. Today, natural products are still predominant sources of antituberculosis agents and remain the mainstays in the current TB drug discovery and development pipeline. In this INBRE pilot project application, we will synthesize, evaluate, and develop macrocyclic wollamide B analogues as novel antituberculosis agents. The specific aim focuses on systematic structure-activity relationship (SAR) studies and evaluating this new chemotype cyclic hexapeptide antibiotics. To achieve these goals, we will collaborate with Dr. Richard Lee (Member, St. Jude Children’s Research Hospital, Memphis, TN) and apply a multidisciplinary collaboration approach with expertise in synthetic organic chemistry, medicinal chemistry, microbiology, and antimicrobial drug discovery and development.