ABSTRACT
(±)-Decumicorine A (1) and (±)-epi-decumicorine A (2), two pairs of enantiomeric isoquinoline alkaloids featuring a novel phenylpropanoid-conjugated protoberberine skeleton, were isolated and purified from the rhizomes of Corydalis decumbens. The separation of (±)-1 and (±)-2 was achieved by chiral HPLC to produce four optically pure enantiomers. The structures and absolute configurations of compounds (-)-1, (+)-1, (-)-2, and (+)-2 were elucidated by spectroscopic analysis, ECD calculations, and X-ray crystallographic analyses. The two racemates were generated from a Diels-Alder [4 + 2] cycloaddition between jatrorrhizine and ferulic acid in the proposed biosynthetic pathways, which were fully verified by a biomimetic synthesis. Moreover, compound (+)-1 exhibited an antiviral entry effect on SARS-CoV-2 pseudovirus by blocking spike binding to the ACE2 receptor on HEK-293T-ACE2h host cells.
Subject(s)
Alkaloids , COVID-19 Drug Treatment , Corydalis , Alkaloids/chemistry , Angiotensin-Converting Enzyme 2 , Antiviral Agents/pharmacology , Berberine Alkaloids , Biomimetics , Corydalis/chemistry , Humans , Isoquinolines , Molecular Structure , Rhizome , SARS-CoV-2ABSTRACT
COVID-19 has become disastrous for world and spread all over. Researchers all around the globe are working to discover a drug to cure from COVID-19. RNA dependent RNA polymerase plays a key role in SARS-CoV-2 replication and thus it could be a potential target for SARS-CoV-2. This study revealed that Protopine, Allocryptopine and (±) 6- Acetonyldihydrochelerythrine could be potential RdRp inhibitors of SARS-CoV-2.