Mehreen Saba, Ali Muhammad Imran, Muntha Sidra Tul, Zia Mehwash, Ullah Aman, Ullah Saeed, Khan Ajmal, Hussain Javid, Anwar Muhammad U, Al-Harrasi Ahmed, Naseer Muhammad Moazzam
Department of Chemistry, Quaid-i-Azam University Islamabad 45320 Pakistan
Department of Chemistry, Faculty of Sciences, The University of Haripur KP 22620 Pakistan.
RSC Adv. 2025 May 7;15(19):14717-14729. doi: 10.1039/d5ra00770d. eCollection 2025 May 6.
Effective α-glucosidase inhibitors are vital for managing type 2 diabetes, emphasizing the need for novel and potent compounds. A series of novel -phenoxyethylisatin hydrazones 1(a-l) have been synthesized and characterized by their spectral data, and in the case of 1l by its single crystal X-ray analysis. All the synthesized compounds were evaluated for their inhibition potential against the α-glucosidase enzyme. Interestingly, most of these compounds exhibited significant inhibitory activity against the α-glucosidase enzyme, with IC values ranging from 3.64 ± 0.13 to 94.89 ± 0.64 μM compared to the standard drug, acarbose (IC = 873.34 ± 1.67 μM). The compound 1e was found to be the most active compound of the series having an IC value of 3.64 ± 0.13 μM. Molecular docking studies revealed a binding score of -9.7 kcal mol for 1e, slightly surpassing that of acarbose (-9.4 kcal mol). Unlike acarbose, which primarily relies on hydrogen bonding, the binding interactions of 1e are dominated by π-interactions. ADMET profiling confirmed favourable pharmacokinetics for these compounds, including good oral bioavailability, balanced hydrophilicity, and minimal predicted toxicity. These findings highlight the potential of these compounds as promising candidates for the development of more effective treatments for hyperglycemia.
有效的α-葡萄糖苷酶抑制剂对2型糖尿病的管理至关重要，这凸显了对新型高效化合物的需求。一系列新型的苯氧乙基异吲哚酮腙1（a - l）已被合成，并通过光谱数据进行了表征，其中1l还通过单晶X射线分析进行了表征。所有合成的化合物都针对其对α-葡萄糖苷酶的抑制潜力进行了评估。有趣的是，这些化合物中的大多数对α-葡萄糖苷酶表现出显著的抑制活性，与标准药物阿卡波糖（IC = 873.34 ± 1.67 μM）相比，其IC值范围为3.64 ± 0.13至94.89 ± 0.64 μM。化合物1e被发现是该系列中活性最高的化合物，IC值为3.64 ± 0.13 μM。分子对接研究表明1e的结合分数为-9.7 kcal/mol，略高于阿卡波糖（-9.4 kcal/mol）。与主要依赖氢键的阿卡波糖不同，1e的结合相互作用以π-相互作用为主。ADMET分析证实这些化合物具有良好的药代动力学性质，包括良好的口服生物利用度、平衡的亲水性和最小的预测毒性。这些发现突出了这些化合物作为开发更有效高血糖治疗方法的有前景候选物的潜力。
