Iridoids from Himatanthus sucuuba Modulate Feeding Behavior of Lutzomyia longipalpis: Integrated Experimental and...

Control strategies for leishmaniasis increasingly target sand fly vectors through sugar feeding approaches containing bioactive compounds. This study investigated the behavioral and toxicological effects of the iridoids plumericin and isoplumericin, isolated from Himatanthus sucuuba, on Lutzomyia longipalpis by integrating computational and experimental approaches focused on gustatory system interactions. The iridoids were purified by column chromatography and characterized by GC-MS. The gustatory receptor A0A1B0CHD5 was structurally characterized through homology modeling, followed by molecular docking and 100 ns molecular dynamics simulations. Behavioral assays evaluated survival, repellency, and feeding preferences using sugar solutions supplemented with an iridoid mixture. Toxicity was assessed in Drosophila melanogaster as a non-target organism model. Molecular docking results revealed comparable binding affinities between sucrose (ChemPLP score 57.96) and the iridoids plumericin (49.08) and isoplumericin (47.75). Molecular dynamics simulations confirmed the stability of the ligand-receptor complexes and revealed distinct conformational changes. The iridoids did not affect L. longipalpis survival, showed no repellency, and did not reduce sugar feeding acceptance. Preference for the control diet was observed only after continuous exposure (48 h), suggesting involvement of post-ingestive sensory processing. No acute toxicity was observed in D. melanogaster (96% survival). These findings demonstrate that iridoids preserve vector feeding behavior and survival while exhibiting low toxicity to non-target organisms, supporting their potential use in gustatory modulation strategies in leishmaniasis vector control without compromising ecological safety.