Department of Chemistry, Government College University Faisalabad, Faisalabad, Pakistan.
J Cell Biochem. 2024 Oct;125(10):e30646. doi: 10.1002/jcb.30646. Epub 2024 Sep 6.
In the current study, new pyrazolo[3,4-b]pyridine esters, hydrazides, and Schiff bases have been synthesized starting from 3-methyl-1-phenyl-1H-pyrazol-5-amine. The first step involved solvent-free synthesis of pyrazolo[3,4-b]pyridine-6-carboxylate derivatives (2a-d) with 55%-70% yield in the minimum time frame compared with the conventional refluxing method, which was followed by the synthesis of corresponding hydrazides (3a-d) and hydrazones (4a-e). The structures of the synthesized derivatives were confirmed using element analysis, FT-IR, H NMR, C NMR, and LC-MS techniques. Synthesized hydrazides (3a-d) and hydrazones (4a-e) were also tested for their in-vitro antidiabetic activity and found that all the compounds exhibited significant antidiabetic activity, while 3c (IC = 9.6 ± 0.5 μM) among the hydrazides and 4c (IC = 13.9 ± 0.7 μM) among the hydrazones were found to be more active in comparison to other synthesized derivatives. These in-vitro results were further validated via docking studies against the α-amylase enzyme using the reference drug acarbose (200.1 ± 10.0 μM). The results were greatly in agreement with their in-vitro studies and these derivatives can be encouraging candidates for further in-vivo studies in mice models.
在当前的研究中，我们以 3-甲基-1-苯基-1H-吡唑-5-胺为起始原料，合成了新的吡唑并[3,4-b]吡啶酯、酰肼和席夫碱。第一步是在无溶剂条件下合成吡唑并[3,4-b]吡啶-6-羧酸酯衍生物（2a-d），与传统回流法相比，收率为 55%-70%，反应时间最短，随后合成相应的酰肼（3a-d）和腙（4a-e）。通过元素分析、FT-IR、H NMR、C NMR 和 LC-MS 技术确认了合成衍生物的结构。合成的酰肼（3a-d）和腙（4a-e）也进行了体外抗糖尿病活性测试，结果表明所有化合物均表现出显著的抗糖尿病活性，其中酰肼（3c，IC=9.6±0.5μM）和腙（4c，IC=13.9±0.7μM）的活性高于其他合成衍生物。这些体外结果通过与参考药物阿卡波糖（200.1±10.0μM）对α-淀粉酶酶的对接研究进一步验证。结果与体外研究非常吻合，这些衍生物可能是进一步在小鼠模型中进行体内研究的有希望的候选物。
