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
| Autor: | Anelia Ts. Mavrova, Diana Wesselinova, Lubomir A. Lubenov, J. A. Tsenov |
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| Rok vydání: | 2014 |
| Předmět: |
Stereochemistry
Cell Survival Antineoplastic Agents Pyrimidinones Thiophenes Cell Line HeLa chemistry.chemical_compound Structure-Activity Relationship Drug Discovery Thiadiazoles Cytotoxic T cell Moiety Humans Cytotoxicity Cell Proliferation Pharmacology biology Dose-Response Relationship Drug Molecular Structure Chemistry Organic Chemistry 1 2 4-Triazole General Medicine Hep G2 Cells Triazoles biology.organism_classification Hep G2 Cell culture Cancer cell Drug Screening Assays Antitumor HT29 Cells HeLa Cells |
| Zdroj: | European journal of medicinal chemistry. 86 |
| ISSN: | 1768-3254 |
| Popis: | 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 IC 50 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 IC 50 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 IC 50 – 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 IC 50 – 0.21 μM. Proliferative effects to Lep 3 demonstrated compounds 5 , 7 – 8 , 11 – 14 , 16 , 18 whose EC 50 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. |
| Databáze: | OpenAIRE |
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