Synthesis of isothio- and isoselenocyanates of adamantane series and their cytotoxic activity

Isothio- and isoselenocyanates of the adamantane series were synthesized in 45–88% yields and were shown to inhibit the growth of the cancer cells lines HCT-116 (colorectal carcinoma), MCF-7 (breast adenocarcinoma), PC-3 (prostate adenocarcinoma), and A549 (lung carcinoma) with half-maximal inhibitory concentrations (IC₅₀) in the range of 1.7–67 µmol L⁻¹. The following structure—activity relationship was established: the inhibitory activity of adamantyl-containing isoselenocyanates 2a–f against the growth of the HCT-116, MCF-7, PC-3, and A549 cancer cell lines decreases with increasing length of the spacer between the adamantane moiety and the isoselenocyanate group, showing a saw-tooth decrease in the activity. The isosteric replacement of a sulfur atom by selenium leads to an increase in the inhibitory activity. Thus, 1-isoselenocyanatoadamantane 2c proved to be three times more active against the growth of the MCF-7 cancer cell line (IC₅₀ = 8.2 µmol L⁻¹) compared to its sulfur-containing analog. This effect noticeably decreases with increasing length of the spacer between the adamantane moiety and the isoselenocyanate group. 1-Isocyanoadamantane 3c, which does not contain a sulfur or selenium atom, inhibits the growth of the HCT-116 cancer cell line (IC₅₀ = 40 µmol L⁻¹) and is not active against the MCF-7, PC-3, and A549 cancer cell lines.