Antimicrobial and anticancer (iso)quinoline alkaloids in plants with antidiarrheal ethnobotanical use: a review of in vitro effects on intestinal bacteria and cells

Abstract Bacterial dysbiosis is a recognized risk of inappropriate antimicrobial treatment of infectious diarrhoea, and its link to gastrointestinal carcinogenesis is increasingly discussed. (Iso)quinolines are plant alkaloids that serve as scaffolds for several antibiotic and anticancer drugs due to their broad biological activities. Moreover, some studies suggest they may have a minimal or non-disruptive impact on the indigenous gut microbiota. Present review evaluates the previously described bioactive properties of 258 plant (iso)quinolines against intestinal diarrheagenic/probiotic bacteria and/or cancer/normal cells in vitro (e.g., minimum inhibitory concentrations, half maximal inhibitory concentrations), based on which it performs structure–activity relationship analyses for each of the involved structural type. Furthermore, it analyses how the abundance of the most active alkaloids in plants relates to their ethnopharmacological importance and traditional use. The results showed that (iso)quinolines of benzophenanthridine, indolo(iso)quinoline, and furoquinoline structures exhibit strong antibacterial and anticancer potential against multiple intestinal targets, whereas specific structural features of Amaryllidaceae isoquinolines, simple quinolines, and protoberberines appear to enhance selectivity by exerting lower effects on normal cells and/or probiotic bacteria. The chemotaxonomic assessment identified several plant genera within Rutaceae, Papaveraceae and other mainly Ranunculales families as important natural sources of these compounds, many of which are traditionally used in treating gastrointestinal disorders. Future research should include (iso)quinolines with identified structural features in broader in vitro assays, advanced microbiota models, in vivo systems, toxicological studies, and detailed phytochemical analyses of their plant sources to better clarify their safety and therapeutic relevance.