Synthesis of Several Cytisine Derivatives and their Cytotoxicities against A431, A375, and HCT 116 Tumor Cell Lines

Abstract

Cytotoxicities of the quinolizidine alkaloid (–)-cytisine and 19 of its derivatives with substituents in the 3-, 9-, and 11-positions were assessed against A431 (epidermal carcinoma), A375 (melanoma), and HCT 116 (colorectal carcinoma) tumor cell lines using the MTT assay (etoposide reference drug). Practically all synthesized compounds at a concentration of 30 μM possessed slight ability to inhibit metabolic activity of these cell lines except benzylcytisine 4, methylcytisines 18 and 19, which contained a phenylurea fragment in the 9- or 11-position of the 2-pyridone core, and 11-chloro adamantylthiocarboxamide 16. Thiocarboxamide 16 reduced A431 cell survival up to 56.06% under the experimental conditions; derivatives 4, 18, and 19, of HCT 116 cell line by 57.52, 58.84, and 56.34%, respectively.