Antiproliferative activities of halogenated thieno[3,2-d]pyrimidines

• Published in: Bioorganic & medicinal chemistry Vol. 22; no. 7; pp. 2113 - 2122
• Main Authors: Temburnikar, Kartik W., Zimmermann, Sarah C., Kim, Nathaniel T., Ross, Christina R., Gelbmann, Christopher, Salomon, Christine E., Wilson, Gerald M., Balzarini, Jan, Seley-Radtke, Katherine L.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.04.2014; Elsevier
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antifungal; Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Bacillus subtilis - drug effects; Biochemistry & Molecular Biology; Cell Cycle - drug effects; Cell Proliferation - drug effects; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Cytostatic; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Fungi - drug effects; Heterocyclic chemistry; Humans; Life Sciences & Biomedicine; Microbial Sensitivity Tests; Molecular Structure; Pharmacology & Pharmacy; Physical Sciences; Pyrimidines - chemical synthesis; Pyrimidines - chemistry; Pyrimidines - pharmacology; Science & Technology; Structure-Activity Relationship; Thieno[3,2-d]pyrimidine; Tumor Cells, Cultured; Thieno[3,2-d]pyrimidine; Heterocyclic chemistry; Antifungal; Cytostatic; Apoptosis; DESIGN; SERIES; KINASE INHIBITOR; CANCER; DISCOVERY; POTENT; PI3 KINASE; BIOLOGICAL EVALUATION; C-NUCLEOSIDE ISOSTERE; DERIVATIVES
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2014.02.033

The in vitro evaluation of thieno[3,2-d]pyrimidines identified halogenated compounds 1 and 2 with antiproliferative activity against three different cancer cell lines. A structure activity relationship study indicated the necessity of the chlorine at the C4-position for biological activity. The two most active compounds 1 and 2 were found to induce apoptosis in the leukemia L1210 cell line. Additionally, the compounds were screened against a variety of other microbial targets and as a result, selective activity against several fungi was also observed. The synthesis and preliminary biological results are reported herein.