Institute of Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam; Graduate University of Science and Technology, VAST, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam.
Institute of Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam.
Bioorg Med Chem Lett. 2024 Jan 15;98:129566. doi: 10.1016/j.bmcl.2023.129566. Epub 2023 Nov 24.
In this study, new indol-fused pyrano[2,3-d]pyrimidines were designed and synthesized. These products were obtained in moderate to good yields and their structures were assigned by NMR, MS, and IR analysis. Afterwards, the biological important of the products was highlighted by evaluating in vitro for α-glucosidase inhibitory activity as well as acetylcholinesterase (AChE) inhibitory activity. Eleven products revealed substantial inhibitory activity against α-glucosidase enzyme, among which, two most potent products 11d,e were approximately 93-fold more potent than acarbose as a standard antidiabetic drug. Besides that, product 11k exhibited good AChE inhibition. The substituents on the 5-phenyl ring, attached to the pyran ring, played a critical role in inhibitory activities. The biological potencies have provided an opportunity to further investigations of indol-fused pyrano[2,3-d]pyrimidines as potential anti-diabetic agents.
在这项研究中，设计并合成了新的吲哚并[2,3-d]嘧啶并吡喃。这些产物以中等至良好的产率得到，并通过 NMR、MS 和 IR 分析确定了它们的结构。随后，通过评估体外α-葡萄糖苷酶抑制活性和乙酰胆碱酯酶（AChE）抑制活性来强调产物的生物重要性。十一种产物对α-葡萄糖苷酶表现出显著的抑制活性，其中两种最有效的产物 11d,e 的抑制活性比阿卡波糖作为标准抗糖尿病药物高约 93 倍。此外，产物 11k 对 AChE 具有良好的抑制作用。连接到吡喃环上的 5-苯基环上的取代基对抑制活性起着关键作用。这些生物活性为进一步研究吲哚并[2,3-d]嘧啶并吡喃作为潜在的抗糖尿病药物提供了机会。
