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

Mellpaladines 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–...

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Published in:Journal of organic chemistry 2024-05, Vol.89 (9), p.5977-5987
Main Authors: Sakai, Ryuichi, Matsumura, Ken, Uchimasu, Hajime, Miyako, Kei, Taniguchi, Tohru, Kovvuri, V. Raghavendra Rao, Acharige, Anjana Delpe, Hull, Kenneth G., Romo, Daniel, Thaveepornkul, Lakkana, Chimnaronk, Sarin, Miyamoto, Hiroko, Takada, Ayato, Watari, Hiromi, Fujita, Masaki J., Sakaue, Jiro
Format: Article
Language:English
Subjects:
Alkaloids - chemical synthesis
Alkaloids - chemistry
Alkaloids - isolation & purification
Alkaloids - pharmacology
Animals
Antiviral Agents - chemical synthesis
Antiviral Agents - chemistry
Antiviral Agents - isolation & purification
Antiviral Agents - pharmacology
Dopamine - chemistry
Dopamine - pharmacology
Guanidine - chemistry
Guanidine - pharmacology
Guanidines - chemistry
Guanidines - isolation & purification
Guanidines - pharmacology
Humans
Mice
Molecular Structure
SARS-CoV-2 - drug effects
Urochordata - chemistry
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Summary:Mellpaladines 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).
ISSN:0022-3263
1520-6904
DOI:10.1021/acs.joc.3c02765