Comparing of compounds 18, 20, 22, and 23 indicated that the cytotoxic activity against SW707, CCRF/CEM, T47D, and P388 were in the order ethoxycarbonyloxy > hydrophthaloyloxy > cinnamoyloxy > benzoyloxy. Whereas the activity of these compounds against B16 was as follows: ethoxycarbonyloxy > cinnamoyloxy > benzoyloxy > hydrophthaloyloxy. It is interesting to note that the acyloxy compounds 16–25, prepared in this study, exhibited the most potent cytotoxicity against cancer cell B16 melanoma. These results may suggest
that 4-acyloxy-2-butynyl function is important for anti-melanoma activity. Another noteworthy feature of the obtained results was the observation that acyloxy compounds 19, selleck kinase inhibitor 21, and 24 exhibited the most potent cytotoxicity with ID50 values <3.1 μg/ml against B16 cancer cell line, among all the compounds (5–25) prepared in this study. The replacement of methyl group by propargyl, compounds 23 and 25, respectively, resulted in decrease of activity. Conclusions Novel acetylenic thioquinolines 6–12 and 16–25, possessing in positions
3 and 4, one or two, propargyl, 4-chloro-2-butynyl, or 4-acyloxy-2-butynyl groups were synthesized in good yields using Ulixertinib nmr 4-chloro-quinoline derivatives 3–5 and 4-hydroxy-2-butynyl derivatives 13–15 as starting material. The obtained OSBPL9 compounds were evaluated for antiproliferative activity in vitro against three human cancer cell lines: SW707 (colorectal cancer), CCRF/CEM (leukemia), T47D (breast cancer) and two murine cancer cell lines: P388 (leukemia), B16 (melanoma). All the tested compounds showed varied activity against different cancer cell lines. As a result of the SAR, it was revealed that the nature of the acetylenic substituent at the C-3 and C-4 positions
and character of the heteroatoms (Se and S) at C-4 critically influence the anticancer activity in vitro of the studied compounds. Among the prepared compounds, 8, 12, and 21 were found to be the most active, with ID50 values ranging from 0.4 to 3.8 μg/ml comparable to that of Ro 61-8048 mw referential anticancer drug, cisplatin. It is of interest to note that the 4-acyloxy-2-butynyl function is important for anti-melanoma activity. The obtained compounds seem to be good candidate for further anticancer activity studies in vitro using a broad panel of human and murine cell lines with the aim to select compounds for studies in vivo. Experimental General techniques Melting points were determined in open capillary tubes on a Boetius melting point apparatus and are uncorrected. 1H NMR (300 MHz) spectra were recorded on a Bruker MSL 300 spectrometer in CDCl3 solvents with tetramethylsilane as internal standard; chemical shifts are reported in ppm (δ) and J values in Hz.