Sakai R.Matsumura K.Uchimasu H.Miyako K.Taniguchi T.Kovvuri V.R.R.Acharige A.D.Hull K.G.Romo D.Thaveepornkul L.Chimnaronk S.Miyamoto H.Takada A.Watari H.Fujita M.J.Sakaue J.Mahidol University2024-04-122024-04-122023-01-01Journal of Organic Chemistry (2023)00223263https://repository.li.mahidol.ac.th/handle/123456789/97935Mellpaladines A-C (1-3) and dopargimine (4) 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 (5), three additional mellpaladines D-F (6-8), and serotodopalgimine (9), along with a dimer of serotonin, 5,5′-dihydroxy-4,4′-bistryptamine (10). The structures of these compounds were determined based on spectrometric and spectroscopic analyses. Compound 4 and its congeners dopargine (11), nordopargimine (15), and 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)ethan-1-amine (16) were synthetically prepared for biological evaluations. The biological activities of all isolated compounds were evaluated in comparison with those of 1-4 using a mouse behavioral assay upon intracerebroventricular injection, revealing key functional groups in the dopargimines and mellpaladines for in vivo 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).ChemistryArticleSCOPUS10.1021/acs.joc.3c027652-s2.0-8518952559215206904