Comprehensive study of alkaloids from Scadoxus multiflorus by HPLC-PDA-SPE-NMR and evaluation of their anti-SARS-CoV-2 activity.

Scadoxus multiflorus (Martyn) Raf. (Amaryllidaceae) is traditionally used for the treatment of many respiratory problems (bronchitis, asthma, pneumonia, etc.). However, the alkaloidal composition of S. multiflorus has rarely been explored. In the present study, a full investigation of bulbs of S. multiflorus was carried out using HPLC-PDA-SPE-NMR, followed by structure elucidation using extensive spectroscopic techniques coupled with DFT calculation. With respect to the indigenous usage of this species for treating respiratory-related problems, antiviral activity against the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) was assessed for all isolated compounds. As a result, a previously undescribed alkaloid, 9- O -demethyl-11-hydroxylgalanthine (or 2- O -methyl-11-hydroxypseudolycorine), together with fourteen known ones were identified. Nine alkaloids, i.e. 2- O -methylpseudolycorine, ungiminorine, ungiminorine N -oxide, 9-de- O -methyl-11β-hydroxygalanthamine, 2-hydroxy- O,N -dimethylnorbelladine, O -demethylmaritidine, 8- O -demethyloxomaritidine, narcissidine, and sanguinine, were reported for the first time in this species. In addition, also lycorine, narciclasine, lycoricidine, montanine and 3- O -acetylsanguinine were obtained. Results showed that 9- O -demethyl-11-hydroxylgalanthine, 8- O -demethyloxomaritidine, 3- O -acetylsanguinine and 9-de- O -methyl-11β-hydroxygalanthamine exhibited weak antiviral activity at non-cytotoxic concentrations (EC 50 of 53, 70, 49, 62 µM, respectively). S. multiflorus appears to be a promising source of anti-SARS-CoV-2 Amaryllidaceae alkaloid scaffolds. [Display omitted] • A new alkaloid was described: 9- O -demethyl-11-hydroxylgalanthine. • Nine alkaloids were reported for the first time in S. multiflorus. • Four alkaloids exhibited weak in vitro anti-SARS-CoV-2 activity (EC50 = 49–70 μM). • Four alkaloids displayed cytotoxicity (CC50 = < 10 μM). [ABSTRACT FROM AUTHOR]