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 mu M possessed slight ability to inhibit metabolic activity of these cell lines except benzylcytisine4, methylcytisines18and19, which contained a phenylurea fragment in the 9- or 11-position of the 2-pyridone core, and 11-chloro adamantylthiocarboxamide16. Thiocarboxamide16reduced A431 cell survival up to 56.06% under the experimental conditions; derivatives4,18, and19, of HCT 116 cell line by 57.52, 58.84, and 56.34%, respectively.