Abstract 1957 Determining Antibacterial Activity of Maleimide-Tryptamine Hybrids

The rapid emergence of antimicrobial resistance due to inappropriate use of FDA-approved antibiotics has prompted the search for multi-mechanistic antimicrobial agents. Molecular hybridization of potential bifunctional antimicrobial compounds offers a path to designing such agents. Molecular hybridization was used to synthesize a series of maleimide-tryptamine hybrids, subsequently screened for antibacterial activity using Kirby Bauer assays. However, the insolubility of the hybrids made it challenging to assess their biological activity. In this study, we used methyl-beta-cyclodextrin (MβCD) as a drug vehicle to solubilize compounds and aid in drug delivery. UV-visible spectroscopy showed that aqueous solubility of MβCD increased in a 10% solution of MβCD. Antibacterial activity against several gram-negative and gram-positive bacteria was determined by bacterial cell growth assays in media containing MβCD (10%). Hybrids showing ≥50% cell death were considered viable leads. The data shows that compounds with functional groups imparting broad-spectrum activity include electron-withdrawing (e.g., nitro), hydrophobic (e.g., methoxy) and lipophilic (e.g., thiomethyl) substituents. Additionally, gram-positive bacteria showed the most significant susceptibility to hybrid compounds compared to gram-negative bacteria. Protein content of each cell line exposed to compound was determined using SDS page gel electrophoresis and the data suggests that there are proteins of interest to target. We would like to thank the Tom Smith Undergraduate Research Fund, the Heyl Science Scholarship Fund, and the Kaufman Research Fund for funding this research over the past three summers.