Pyridothiadiazine derivatives as aldose reductase inhibitors having antioxidant activity

• Published in: Journal of enzyme inhibition and medicinal chemistry Vol. 31; no. sup1; pp. 126 - 130
• Main Authors: Zhu, Shaojuan, Zhang, Shuzhen, Hao, Xin, Qin, Xiangyu, Parveen, Shagufta, Yang, Shaoqi, Ma, Bing, Zhu, Changjin
• Format: Journal Article
• Language: English
• Published: ABINGDON Taylor & Francis 01.11.2016
• Subjects: Aldehyde Reductase - antagonists & inhibitors; Aldehyde Reductase - metabolism; Aldose reductase inhibitors; antioxidant activity; Antioxidants - chemical synthesis; Antioxidants - chemistry; Antioxidants - pharmacology; Biochemistry & Molecular Biology; Chemistry, Medicinal; Dose-Response Relationship, Drug; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Humans; Life Sciences & Biomedicine; Molecular Docking Simulation; Molecular Structure; Pharmacology & Pharmacy; pyridothiadiazine derivatives; Science & Technology; Structure-Activity Relationship; structure-activity relationships; Thiadiazines - chemical synthesis; Thiadiazines - chemistry; Thiadiazines - pharmacology; OXIDATIVE STRESS; POTENT; Aldose reductase inhibitors; structure-activity relationships; antioxidant activity; pyridothiadiazine derivatives
• ISSN: 1475-6366; 1475-6374
• DOI: 10.1080/14756366.2016.1178638

A series of aldose reductase (ALR2) inhibitors based on pyridothiadiazine were prepared and evaluated for their activities in ALR2 inhibition, DPPH scavenging, and MDA inhibition. Comparison studies were carried out between analogs having either hydroxyl or methoxy groups substituted on the N2-benzyl side chains of the compounds. Most of the hydroxy-substituted compounds were found to be more potent compared to their methoxy-substituted analogs with respect to DPPH inhibition (>93%) and MDA inhibition (>73%). However, ALR2 inhibitory activity was found to be affected by the electron-withdrawing substituent at the C7 position in addition to the effect of the N2-substituted benzyl group. These results provide an array of multifunctional ALR2 inhibitors possessing capacities both for ALR2 inhibition and as antioxidants.