Monoterpene Indole Alkaloids with Antimicrobial Activity Against Helicobacter pylori

<i>Helicobacter pylori</i> infection, a leading cause of gastric ulcers and gastric cancer, presents a major health challenge, exacerbated by rising antibiotic resistance. This study investigated the antibacterial potential of plant-derived compounds, isolated from different plant species, against <i>H. pylori</i>. Thus, a library of 153 natural compounds and derivatives, including monoterpene indole and bisindole alkaloids, obtained from the African medicinal plant <i>Tabernaemontana elegans</i> was screened in vitro for minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against <i>H. pylori</i>. Active compounds (<b>1</b>-<b>7</b>) were tested for anti-biofilm activity and cytotoxicity on VERO cells to determine their half-maximal cytotoxic concentrations (CC₅₀). Six monoterpene indole alkaloid azine derivatives (<b>1</b>-<b>6</b>) and vobasinyl-iboga type bisindole alkaloid (<b>7</b>) displayed antibacterial activity, with MICs between 10 and 20 µM. Compounds <b>2</b>, <b>3</b>, and <b>6</b> exhibited bactericidal activity, with MBCs of 20 µM. Notably, compounds <b>1</b> to <b>4</b> inhibited <i>H. pylori</i> biofilm formation at sub-inhibitory concentrations. Cytotoxicity assays revealed CC₅₀ values above MICs, indicating a favorable safety profile for potential therapeutic use. This study highlights the potential of <i>T. elegans</i> monoterpene indole alkaloids as antibacterial agents and supports further exploration of plant-derived compounds as alternative treatments for <i>H. pylori</i>, offering a promising approach to address antibiotic resistance in gastrointestinal diseases.