Dopamine-Derived Guanidine Alkaloids from a Didemnidae Tunicate: Isolation, Synthesis, and Biological Activities.

Mellpaladines A-C () and dopargimine () are dopamine-derived guanidine alkaloids isolated from a specimen of Palauan Didemnidae tunicate as possible modulators of neuronal receptors. In this study, we isolated the dopargimine derivative 1-carboxydopargimine (), three additional mellpaladines D-F (), and serotodopalgimine (), along with a dimer of serotonin, 5,5'-dihydroxy-4,4'-bistryptamine (). The structures of these compounds were determined based on spectrometric and spectroscopic analyses. Compound and its congeners dopargine (), nordopargimine (), and 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)ethan-1-amine () were synthetically prepared for biological evaluations. The biological activities of all isolated compounds were evaluated in comparison with those of using a mouse behavioral assay upon intracerebroventricular injection, revealing key functional groups in the dopargimines and mellpaladines for behavioral toxicity. Interestingly, these alkaloids also emerged during a screen of our marine natural product library aimed at identifying antiviral activities against dengue virus, SARS-CoV-2, and vesicular stomatitis Indiana virus (VSV) pseudotyped with Ebola virus glycoprotein (VSV-ZGP).