Design and diversity-oriented synthesis of novel 1,4-thiazepan-3-ones fused with bioactive heterocyclic skeletons and evaluation of their antioxidant and cytotoxic activities

• Published in: Bioorganic & medicinal chemistry letters 2012-01, Vol.22 (1), p.743-746
• Main Authors: Shi, Feng, Zeng, Xiao-Ning, Cao, Xu-Dong, Zhang, Shu, Jiang, Bo, Zheng, Wei-Fa, Tu, Shu-Jiang
• Format: Article
• Language: English
• Subjects: 1,4-Thiazepine; Antineoplastic Agents - pharmacology; Antioxidant activity; antioxidants; Antioxidants - pharmacology; Biological and medical sciences; Carbazoles - chemistry; carcinoma; Cell Line, Tumor; Chemistry, Pharmaceutical - methods; Cytotoxicity; Drug Design; Drug Screening Assays, Antitumor - methods; HCT116 Cells; Humans; Medical sciences; microwave treatment; Microwaves; Models, Chemical; Multicomponent reactions; Pharmacology. Drug treatments; Pyrazoles - chemistry; Solvents; Temperature; Thiazepines - chemical synthesis; Thiazepines - pharmacology
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2011.09.081

A series of new 1,4-thiazepan-3-ones with structural diversity were synthesized via three-component reactions and found to have significant antioxidant activity and remarkably selective cytotoxicity to carcinoma cell line HCT 116. This study has achieved the design and diversity-oriented synthesis of novel 1,4-thiazepine derivatives embedded with carbazole, pyrazole or isoxazole motif via microwave-assisted multicomponent reactions under solvent-free condition, thus providing a green and facile access to 1,4-thiazepine derivatives with prominent features of high structural diversity, short reaction time, high yields and environmental friendliness. More importantly, these novel compounds have been subjected to the test of in vitro antioxidant and cytotoxic activities, resulting in the finding that these 1,4-thiazepine derivatives not only have significant antioxidant activity, but also exhibit remarkably selective cytotoxicity to carcinoma cell line HCT 116.