Expansion, Synthesis, and Biological Evaluation of a Focused Library of N-Substituted Indolines and 1,2,3,4-Tetrahyrdoquinolines as Antimicrobials

Infectious diseases and their resistance to common antibiotics are a growing source of concern, affecting hundreds of millions of people across the globe. New classes of antibiotics with novel mechanisms of action are imperative for treating infections resistant to the current therapies available. In previous work, a library of related N-substituted heterocycles was synthesized and assessed for antimicrobial activity with promising results. Building on these encouraging results, a library of sixteen N-benzenesulfonyl indoline-2-carboxylic acid derivatives was synthesized via one-pot parallel synthesis. Each compound was characterized via NMR, LCMS, melting point, and IR, and yields were consistently above 75%. Preliminary minimum inhibitory concentration (MIC) data suggest that the active compounds have an inhibitory effect (64 µg/mL) against S. aureus. Similarly, mammalian cytotoxicity assays showed minimal toxicity at concentrations as high as 512 µg/mL