Synthesis of Novel Analogs of Thieno[2,3-d] Pyrimidin-4(3H)-ones as Selective Inhibitors of Cancer Cell Growth

• Published in: Biomolecules (Basel, Switzerland) Vol. 9; no. 10; p. 631
• Main Authors: Zhang, Sheng, Liu, Feize, Hou, Xueling, Cao, Jianguo, Dai, Xiling, Yu, Junjie, Huang, Guozheng
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 21.10.2019; MDPI AG
• Subjects: anticancer; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Cell Proliferation - drug effects; Cells, Cultured; Drug Screening Assays, Antitumor; Humans; Neoplasms - pathology; Pyrimidinones - chemical synthesis; Pyrimidinones - chemistry; Pyrimidinones - pharmacology; thieno[2,3-d] pyrimidinone; thienopyrimidine; thienopyrimidine; thieno[2,3-d] pyrimidinone; anticancer
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom9100631

New 2,3-disubstituted thieno[2,3-d]pyrimidin-4(3H)-ones were synthesized via a one-pot reaction from 2H-thieno[2,3-d] [1,3]oxazine-2,4(1H)-diones, aromatic aldehydes, and benzylamine or 4-hydroxylbezylamine. The obtained compounds were tested in vitro for cancer cell growth inhibition. Compound 19 can inhibit all four types of tested cancer cells, i.e., MCF-7, A549, PC-9, and PC-3 cells. Most of the compounds inhibited the proliferation of A549 and MCF-7 cells. Compound 15 exhibited the strongest anti-proliferative effect against A549 cell lines with IC50 values of 0.94 μM, and with no toxicity to normal human liver cells. Its potency was further proved by cell clone formation assay, Hoechst 33258 staining, and evaluation on the effects of apoptosis-related proteins.