Synthesis and antiproliferative activity of some new thieno[2,3-d]pyrimidin-4(3H)-ones containing 1,2,4-triazole and 1,3,4-thiadiazole moiety

• Synthesis of new thieno[2,3-d]pyrimidin-4(3H)-ones was optimized.
• Eight of the compounds demonstrated IC50 in the range 9.3–9.5·10−4 μM to HeLa cells.
• Some of the compounds exhibited cytotoxicity against HT-29 and MDA-MB-231 cells.
• Cytotoxicity to Hep G2 showed six of the compounds.
• Most of the compounds revealed proliferative activities to Lep3 cells.

Some new thieno[2,3-d]pyrimidin-4(3H)-ones containing 1,2,4-triazole and 1,3,4-thiadiazole moiety were synthesized using thieno[2,3-d]pyrimidin-3(4H)-yl)acetohydrazides as precursors in order to determine their cytotoxicity. Compounds 5, 7–8 and 10–18 were evaluated for their cytotoxical effect on four cancer cell lines: human colorectal cancer cell line HT-29, breast cancer cells MDA-MB-231, cervical cancer cells HeLa, human liver carcinoma HepG2 and human normal diploid cell line Lep3. Exclusively high cytotoxic activity of compounds 8, 16 and 17 against MDA-MB-231 cells was ascertained and the calculated IC50 values were 3.91·10−2, 1.2·10−3 and 3.74·10−2 μM respectively. Thienopyrimidinones 10, 15 and 17 exhibited high cytotoxicity against HT-29 cell and the IC50 values were in the range 1.56·10−3 μM– 0.13 μM. To HeLa cell lines cytotoxicity demonstrated compounds 8, 10, 11, 13 and 15–18 but the substance 13 was the most toxic with IC50 – 9.5·10−4 μM. Distinctly high antiproliferative activity of derivatives 10, 14–15 and 17–18 was estimated against Hep G2, compound 15 showed IC50 – 0.21 μM. Proliferative effects to Lep 3 demonstrated compounds 5, 7–8, 11–14, 16, 18 whose EC50 values were from 0.12 to 2.21 μM. The biological data highlighted that the nature and the position of the substituents influence both the cytotoxicity to the cancer cells and the proliferation properties to Lep3 of the tested compounds.

Novel thieno[2,3-d]pyrimidin-4(3H)-ones containing 1,2,4-triazole and 1,3,4-thiadiazole moiety were synthesized and evaluated for their cytotoxicity.Figure optionsDownload as PowerPoint slide