Chemoinformatic analysis of alkaloids of <i>Datura metel</i> and <i>Datura stramonium</i> species: insights from chemical space and diversity analysis

Datura, a widely cultivated plant of the Solanaceae family, is well known for its medicinal properties. Among the various Datura species found globally, <i>Datura metel</i> L. and <i>Datura stramonium</i> L. have garnered significant research interest due to their historical transoceanic connections between the Old and New World. The alkaloids present in Datura exhibit notable ethnobotanical and medicinal properties. This study employs chemoinformatics analysis on 46 and 49 screened alkaloids from <i>D. metel</i> and <i>D. stramonium</i>, respectively, to explore their chemical space, scaffold diversity, protein target interactions, and toxicity profiles. Additionally, chemical similarity analysis with FDA-approved drugs identified 10 alkaloids, predominantly belonging to the tropane-class, with potential drug-like properties. The scaffold 'N1C2CCCC1CC2' emerged as a key structural motif with promising lead-like characteristics for future drug-design efforts. Modifying-enzymes and transmembrane signal-receptors are major interacting proteins, with pathway analysis underscoring their neuromodulatory role. These findings pave the way for their application in drug-discovery.