新型苯并二氧杂环丁烷衍生物的特征描述和抗糖尿病作用研究：动物模型中的体外和体内研究。

Characterization and Investigation of Novel Benzodioxol Derivatives as Antidiabetic Agents: An In Vitro and In Vivo Study in an Animal Model.

机构信息

Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus 00970, Palestine.

Department of Chemistry, Faculty of Sciences, An-Najah National University, Nablus 00970, Palestine.

出版信息

Biomolecules. 2023 Oct 6;13(10):1486. doi: 10.3390/biom13101486.

In this study, we synthesized benzodioxol carboxamide derivatives and investigated their antidiabetic potential. The synthesized compounds ( and ) underwent characterization via HRMS, H-, CAPT-NMR, and MicroED. Their efficacy against α-amylase was assessed in vitro, while MTS assays were employed to gauge cytotoxicity across cancer and normal cell lines. Additionally, the antidiabetic impact of compound was evaluated in vivo using a streptozotocin-induced diabetic mice model. Notably, and displayed potent α-amylase inhibition (IC values of 0.85 and 0.68 µM, respectively) while exhibiting a negligible effect on the Hek293t normal cell line (IC > 150 µM), suggesting their safety. Compound demonstrated significant activity against four cancer cell lines (26-65 µM). In vivo experiments revealed that five doses of substantially reduced mice blood glucose levels from 252.2 mg/dL to 173.8 mg/dL in contrast to the control group. The compelling in vitro anticancer efficacy of and its safety for normal cells underscores the need for further in vivo assessment of this promising compound. This research highlights the potential of benzodioxol derivatives as candidates for the future development of synthetic antidiabetic drugs.

在这项研究中，我们合成了苯并二氧杂环丁酰胺衍生物，并研究了它们的抗糖尿病潜力。合成的化合物（和）通过高分辨质谱（HRMS）、H-NMR、CAPT-NMR 和微 ED 进行了表征。它们对α-淀粉酶的体外抑制活性进行了评估，而 MTS 测定则用于评估在癌细胞和正常细胞系中的细胞毒性。此外，还在链脲佐菌素诱导的糖尿病小鼠模型中评估了化合物在体内的抗糖尿病作用。值得注意的是，和对α-淀粉酶具有很强的抑制作用（IC 值分别为 0.85 和 0.68 µM），而对 Hek293t 正常细胞系的影响可以忽略不计（IC > 150 µM），这表明它们的安全性。化合物对四种癌细胞系（26-65 µM）具有显著的活性。体内实验表明，与对照组相比，五个剂量的显著降低了小鼠的血糖水平，从 252.2 mg/dL 降低到 173.8 mg/dL。和在体外具有很强的抗癌活性，对正常细胞安全，这突出了进一步评估这种有前途的化合物的体内活性的必要性。这项研究强调了苯并二氧杂环丁酰胺衍生物作为未来合成抗糖尿病药物候选物的潜力。