Anti-SARS-CoV-2 Activity and Cytotoxicity of Amaryllidaceae Alkaloids from <i>Hymenocallis littoralis</i>
Ngoc-Thao-Hien Le,
Steven De Jonghe,
Kristien Erven,
Tom Vermeyen,
Aliou M. Baldé,
Wouter A. Herrebout,
Johan Neyts,
Christophe Pannecouque,
Luc Pieters,
Emmy Tuenter
Affiliations
Ngoc-Thao-Hien Le
Natural Products and Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium
Steven De Jonghe
Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Herestraat 49, B-3000 Leuven, Belgium
Kristien Erven
Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Herestraat 49, B-3000 Leuven, Belgium
Tom Vermeyen
Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium
Aliou M. Baldé
Department of Pharmacy, University Gamal Abdel Nasser of Conakry, Conakry 00224, Guinea
Wouter A. Herrebout
Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium
Johan Neyts
Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Herestraat 49, B-3000 Leuven, Belgium
Christophe Pannecouque
Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Herestraat 49, B-3000 Leuven, Belgium
Luc Pieters
Natural Products and Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium
Emmy Tuenter
Natural Products and Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium
The Amaryllidaceae species are well-known as a rich source of bioactive compounds in nature. Although Hymenocallis littoralis has been studied for decades, its polar components were rarely explored. The current phytochemical investigation of Amaryllidaceae alkaloids from H. littoralis led to the identification of three previously undescribed compounds: O-demethyl-norlycoramine (1), (−)-2-epi-pseudolycorine (2) and (+)-2-epi-pseudolycorine (3), together with eight known compounds: 6α-hydroxyhippeastidine (4), 6β-hydroxyhippeastidine (5), lycorine (6), 2-epi-lycorine (7), zephyranthine (8), ungeremine (9), pancratistatin (10) and 9-O-demethyl-7-O-methyllycorenine (11). Among the eight previously reported compounds, five were isolated from H. littoralis for the first time (compounds 4, 5, 7, 8, and 9). Compounds 1, 4, 5, 7, 8, and 11 exhibited weak anti-SARS-CoV-2 activity (EC50 = 40–77 µM) at non-cytotoxic concentrations. Assessment of cytotoxicity on the Vero-E6 cell line revealed lycorine and pancratistatin as cytotoxic substances with CC50 values of 1.2 µM and 0.13 µM, respectively. The preliminary structure-activity relationship for the lycorine-type alkaloids in this study was further investigated, and as a result ring C appears to play a crucial role in their anti-SARS-CoV-2 activity.
