Dipartimento di Scienze Chimiche, Università di Napoli Federico II, Complesso Universitario Monte Sant'Angelo, 80126 Napoli, Italy.
Département de Chimie, Biochimie et Physique, Université du Québec à Trois-Rivières, Trois-Rivières, QC G8Z 4M3, Canada.
Toxins (Basel). 2022 Apr 7;14(4):262. doi: 10.3390/toxins14040262.
Ten Amaryllidaceae alkaloids (AAs) were isolated for the first time from Pancratium maritimum collected in Calabria region, Italy. They belong to different subgroups of this family and were identified as lycorine, which is the main alkaloid, 9-O-demethyllycorine, haemanthidine, haemanthamine, 11-hydroxyvittatine, homolycorine, pancracine, obliquine, tazettine and vittatine. Haemanthidine was isolated as a scalar mixture of two 6-epimers, as already known also for other 6-hydroxycrinine alkaloids, but for the first time they were separated as 6,11-O,O′-di-p-bromobenzoyl esters. The evaluation of the cytotoxic and antiviral potentials of all isolated compounds was undertaken. Lycorine and haemanthidine showed cytotoxic activity on Hacat cells and A431 and AGS cancer cells while, pancracine exhibited selective cytotoxicity against A431 cells. We uncovered that in addition to lycorine and haemanthidine, haemanthamine and pancracine also possess antiretroviral abilities, inhibiting pseudotyped human immunodeficiency virus (HIV)−1 with EC50 of 25.3 µM and 18.5 µM respectively. Strikingly, all the AAs isolated from P. maritimum were able to impede dengue virus (DENV) replication (EC50 ranged from 0.34−73.59 µM) at low to non-cytotoxic concentrations (CC50 ranged from 6.25 µM to >100 µM). Haemanthamine (EC50 = 337 nM), pancracine (EC50 = 357 nM) and haemanthidine (EC50 = 476 nM) were the most potent anti-DENV inhibitors. Thus, this study uncovered new antiviral properties of P. maritimum isolated alkaloids, a significant finding that could lead to the development of new therapeutic strategies to fight viral infectious diseases.
首次从意大利卡拉布里亚地区采集的海葱中分离出 10 种石蒜科生物碱（AAs）。它们属于该科的不同亚科，分别鉴定为石蒜碱（lycorine），这是主要的生物碱，9-O-去甲基石蒜碱（9-O-demethyllycorine），血根碱（haemanthidine），血根碱（haemanthamine），11-羟基维替汀（11-hydroxyvittatine），同源石蒜碱（homolycorine），海葱碱（pancracine），斜方石蒜碱（obliquine），茶亭碱（tazettine）和维替汀（vittatine）。血根碱（haemanthidine）是作为两种 6-差向异构体的混合物分离出来的，正如其他 6-羟基血根碱生物碱（crinine alkaloids）已知的那样，但这是首次将其分离为 6,11-O,O′-二对溴苯甲酰酯。所有分离化合物的细胞毒性和抗病毒潜力的评估都进行了。石蒜碱和血根碱在 Hacat 细胞和 A431 和 AGS 癌细胞中表现出细胞毒性，而海葱碱则对 A431 细胞表现出选择性细胞毒性。我们发现，除了石蒜碱和血根碱外，血根碱（haemanthamine）和海葱碱（pancracine）还具有抗逆转录病毒的能力，对假型人免疫缺陷病毒（HIV）-1 的 EC50 分别为 25.3 µM 和 18.5 µM。值得注意的是，从海葱中分离得到的所有 AAs 都能够在低至非细胞毒性浓度下抑制登革热病毒（DENV）复制（EC50 范围为 0.34-73.59 µM）（CC50 范围为 6.25 µM 至>100 µM）。血根碱（haemanthamine，EC50 = 337 nM），海葱碱（pancracine，EC50 = 357 nM）和血根碱（haemanthidine，EC50 = 476 nM）是最有效的抗 DENV 抑制剂。因此，这项研究揭示了海葱中分离出的生物碱的新的抗病毒特性，这一重要发现可能导致开发新的治疗策略来对抗病毒性传染病。
