Alkaloids from Hippeastrum morelianum Lem. (Amaryllidaceae).

The Amaryllidaceae family has proven to be a rich source of active molecules. As part of an ongoing project, we report a phytochemical study of Hippeastrum morelianum (Amaryllidaceae), from which we have isolated two homolycorine-type alkaloids, the new 2α,7-dimethoxyhomolycorine (1) and the poorly described candimine (2), as well as six known alkaloids: tazettine, pretazettine, 3-epimacronine, haemanthamine, hamayne and trisphaeridine. For reference purposes, the NMR of the isolated compounds was unequivocally described, based on 2D NMR measurements including (1)H-(1)H COSY, (1)H-(1)H NOESY, HSQC and HMBC.

Cytotoxic and Genotoxic Activities of Alkaloids from the Bulbs of Griffinia gardneriana and Habranthus itaobinus (Amaryllidaceae).

BACKGROUND: Amaryllidaceae plants are known to be a great source of alkaloids, which are considered an extensive group of compounds encompassing a wide range of biological activities. The remarkable cytotoxic activities observed in most of the Amaryllidaceae alkaloids derivatives have prompt the chemical and biological investigations in unexplored species from Brazil. OBJECTIVE: To evaluate the cytotoxic and genotoxic properties of alkaloids of Griffinia gardneriana and Habranthus itaobinus bulbs and study the role of caspase-3 as a molecular apoptosis mediator. METHODS: Methanolic crude extracts of Griffinia gardneriana and Habranthus itaobinus bulbs were submitted to acid-base extraction to obtain alkaloid-enriched fractions. The obtained fractions were fractionated using chromatographic techniques leading to isolation and identification of some alkaloids accomplished via HPLC and 1H-NMR, respectively. Molecular docking studies assessed the amount of free binding energy between the isolated alkaloids with the caspase-3 protein and also calculated the theoretical value of Ki. Studies have also been developed to evaluate in vitro cytotoxicity and genotoxicity in such alkaloids and apoptosis activation via the caspase pathway using both tumor and normal cell lines. RESULTS: Seven alkaloids were isolated and identified. Among these, 11-hydroxyvittatine and 2-α-7- dimethoxyhomolycorine were not cytotoxic, whereas tazettine, trisphaeridine, and sanguinine only showed activity against the fibroblast lineage. Lycorine and pretazettine were 10 to 30 folds more cytotoxic than the other alkaloids, including cancerous lines, and were genotoxic and capable of promoting apoptosis via the caspase-3 pathway. This result supports data obtained in docking studies wherein these two compounds exhibited the highest free energy values. CONCLUSION: The cytotoxicity assay revealed that, among the seven alkaloids isolated, only lycorine and pretazettine were active against different cell lines, exhibiting concentration- and time-dependent cytotoxic actions alongside genotoxic action and the ability to induce apoptosis by caspase-3, a result consistent with those obtained in docking studies.

Lycorine derivatives against Trichomonas vaginalis.

Six lycorine derivatives were prepared, characterized, and evaluated for their in vitro anti-Trichomonas vaginalis activity. Compounds bearing an acetyl (2), lauroyl (3), benzoyl (4 and 5), and p-nitrobenzoyl (6 and 7) groups were synthesized. The best activity was achieved with lycorine esterified at C-2 position with lauroyl group. Preliminary structure-activity relationship points that unprotected OH group at C-1 and C-2 is not necessary to the antiparasitic activity, and none of the derivative was less active than lycorine. The lycorine structural requisites required to kill this amitochondriate cell seem to be different in comparison with the derivatives most active against other parasites and tumor cell lines, both mitochondriated cells. This result is an important contribution with our ongoing studies regarding the mechanism of action of the Amaryllidaceae alkaloids on T. vaginalis cell death opening a new perspective to optimize this innovative pharmacological potential.