Semi-synthetic derivatives of Amaryllidaceae alkaloid ambelline as potential lead structures for drug development

Amaryllidaceae alkaloid ambelline, belonging to the crinane-type subgroup, lacks any significant biological activity. However, its analogs prepared by the C-11 hydroxyl groupʼs derivatization possess various pharmacological properties.

Within the current study, thirty-two derivatives were developed and tested for inhibitory activity of cholinesterases and in vitro cytotoxicity to screen their biological activity.

Seven aromatic derivatives with different substitutions on the attached aromatic ring showed inhibitory potency against hBuChE (IC₅₀ < 5 µM), of which 11-O-(1-naphtoyl) ambelline (26) was the most promising, with an IC₅₀ value of 0.10 ± 0.01 µM.

The cytotoxic potential of all derivatives was determined on a panel of nine human cancer cell lines and one noncancerous cell line. 11-O-(4-chloro-3-nitrobenzoyl) ambelline (32) had the most satisfactory cytotoxic potency among the ambelline derivatives, with IC₅₀ ranging from 0.6 ± 0.1 µM (MCF-7) to 9.9 ± 0.2 µM (PANC-1). Derivative 32 was active even against resistant tumor cell lines, such as HT-29 and PANC-1. The most active selective inhibitors of hBuChE are not cytotoxic and could be used as lead structures for a new series of ambelline derivatives, hence the need for further research.

• Reference

• 1 Maříková J, Ritomská A, Korábečný J. et al. Aromatic Esters of the Crinane Amaryllidaceae Alkaloid Ambelline as Selective Inhibitors of Butyrylcholinesterase. J Nat Prod 2020; 83: 1359-1367

Publikationsverlauf

Artikel online veröffentlicht:
12. Dezember 2022