Abstract

In the present study, a series of azo derivatives (TR-1 to TR-9) have been synthesised via the diazo-coupling approach between substituted aromatic amines with phenol or naphthol derivatives. The compounds were evaluated for their therapeutic applications against alpha-glucosidase (anti-diabetic) and pathogenic bacterial strains E. coli (gram-negative), S. aureus (gram-positive), S. aureus (gram-positive) drug-resistant strain, P. aeruginosa (gram-negative), P. aeruginosa (gram-negative) drug-resistant strain and P. vulgaris (gram-negative). The IC₅₀ (µg/mL) of TR-1 was found to be most effective (15.70 ± 1.3 µg/mL) compared to the reference drug acarbose (21.59 ± 1.5 µg/mL), hence, it was further selected for the kinetic studies in order to illustrate the mechanism of inhibition. The enzyme inhibitory kinetics and mode of binding for the most active inhibitor (TR-1) was performed which showed that the compound is a non-competitive inhibitor and effectively inhibits the target enzyme by binding to its binuclear active site reversibly.

摘要

在本研究中，通过取代芳香胺与苯酚或萘酚衍生物之间的重氮偶联方法合成了一系列偶氮衍生物（TR-1至TR-9）。评估了这些化合物对 α-葡萄糖苷酶（抗糖尿病）和致病细菌菌株大肠杆菌（革兰氏阴性）、金黄色葡萄球菌（革兰氏阳性）、金黄色葡萄球菌（革兰氏阳性）耐药性的治疗应用菌株、铜绿假单胞菌（革兰氏阴性）、铜绿假单胞菌（革兰氏阴性）耐药菌株和普通假单胞菌（革兰氏阴性）。TR-1的 IC ₅₀ (µg/mL)发现与参考药物阿卡波糖 (21.59 ± 1.5 µg/mL) 相比最有效 (15.70 ± 1.3 µg/mL)，因此，进一步选择它进行动力学研究以说明抑制机制。对活性最强的抑制剂 ( TR-1 )的酶抑制动力学和结合方式进行了研究，结果表明该化合物是一种非竞争性抑制剂，通过可逆地与其双核活性位点结合来有效抑制目标酶。