Synthesis of benzothiadiazine derivatives exhibiting dual activity as aldose reductase inhibitors and antioxidant agents

• Published in: Bioorganic & medicinal chemistry letters Vol. 26; no. 12; pp. 2880 - 2885
• Main Authors: Zhu, Shaojuan, Hao, Xin, Zhang, Shuzhen, Qin, Xiangyu, Chen, Xin, Zhu, Changjin
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.06.2016; Elsevier
• Subjects: Aldehyde Reductase - antagonists & inhibitors; Aldehyde Reductase - metabolism; Aldose reductase; Antioxidant activity; Antioxidants - chemical synthesis; Antioxidants - chemistry; Antioxidants - pharmacology; Benzothiadiazine derivatives; Benzothiadiazines - chemical synthesis; Benzothiadiazines - chemistry; Benzothiadiazines - pharmacology; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Dose-Response Relationship, Drug; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Humans; Life Sciences & Biomedicine; Molecular Structure; Pharmacology & Pharmacy; Physical Sciences; Science & Technology; Structure-Activity Relationship; Aldose reductase; Benzothiadiazine derivatives; Antioxidant activity; OXIDATIVE STRESS; POTENT
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2016.04.047

[Display omitted] Several multifunctional benzothiadiazine derivatives were synthesized and examined for their inhibition to the enzyme aldose reductase and in vitro antioxidant activity to identify novel drugs for diabetes and its complications. Most of them exhibited good inhibitory activity. Importantly, a number of compounds demonstrated strong antioxidant activity and one compound in particular was extremely active in the DPPH radical scavenging and MDA inhibition analysis. The DPPH radical scavenging rate with this compound was 98.0%, 92.3% and 42.1% at concentrations of 100μM, 10μM, and 1μM, respectively, and the initial reaction rate was faster than Trolox at a concentration of 10μM.