Dopamine-Derived Guanidine Alkaloids from a Didemnidae Tunicate: Isolation, Synthesis, and Biological Activities
Issued Date
2023-01-01
Resource Type
ISSN
00223263
eISSN
15206904
Scopus ID
2-s2.0-85189525592
Journal Title
Journal of Organic Chemistry
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Organic Chemistry (2023)
Suggested Citation
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. Dopamine-Derived Guanidine Alkaloids from a Didemnidae Tunicate: Isolation, Synthesis, and Biological Activities. Journal of Organic Chemistry (2023). doi:10.1021/acs.joc.3c02765 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/97935
Title
Dopamine-Derived Guanidine Alkaloids from a Didemnidae Tunicate: Isolation, Synthesis, and Biological Activities
Corresponding Author(s)
Other Contributor(s)
Abstract
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).