Monoterpene Indole Alkaloids with Antimicrobial Activity Against Helicobacter pylori

Helicobacter pylori 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 H. pylori. Thus, a library of 153 natural compounds and derivatives, including monoterpene indole and bisindole alkaloids, obtained from the African medicinal plant Tabernaemontana elegans was screened in vitro for minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against H. pylori. Active compounds (1-7) 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 (1-6) and vobasinyl-iboga type bisindole alkaloid (7) displayed antibacterial activity, with MICs between 10 and 20 µM. Compounds 2, 3, and 6 exhibited bactericidal activity, with MBCs of 20 µM. Notably, compounds 1 to 4 inhibited H. pylori 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 T. elegans monoterpene indole alkaloids as antibacterial agents and supports further exploration of plant-derived compounds as alternative treatments for H. pylori, offering a promising approach to address antibiotic resistance in gastrointestinal diseases.