Abstract：
Environment-benign, multicomponent synthetic methodologies are vital in modern pharmaceutical research and facilitates multi-targeted drug development via synergistic approach. Herein, we reported green and efficient synthesis of pyrano[2,3-c]pyrazole fused spirooxindole linked 1,2,3-triazoles using a tea waste supported copper catalyst (TWCu). The synthetic approach involves a one-pot, five-component reaction using N-propargylated isatin, hydrazine hydrate, ethyl acetoacetate, malononitrile/ethyl cyanoacetate and aryl azides as model substrates. Mechanistically, the reaction was found to proceed via in situ pyrazolone formation followed by Knoevenagel condensation, azide alkyne cycloaddition and Michael\'s addition reactions. The molecules were developed using structure-based drug design. The primary goal is to identifying anti-oxidant molecules with potential ability to modulate α-amylase and DPP4 (dipeptidyl-peptidase 4) activity. The anti-oxidant analysis, as determined via DPPH, suggested that the synthesized compounds, A6 and A10 possessed excellent anti-oxidant potential compared to butylated hydroxytoluene (BHT). In contrast, compounds A3, A5, A8, A9, A13, A15, and A18 were found to possess comparable anti-oxidant potential. Among these, A3 and A13 possessed potential α-amylase inhibitory activity compared to the acarbose, and A3 further emerged as dual inhibitors of both DPP4 and α-amylase with anti-oxidant potential. The relationship of functionalities on their anti-oxidant and enzymatic inhibition was explored in context to their SAR that was further corroborated using in silico techniques and enzyme kinetics.
摘要：
环境良性，多组分合成方法学在现代药物研究中至关重要，并通过协同方法促进多靶向药物的开发。在这里，我们报道了使用茶废料负载铜催化剂（TWCu）绿色高效地合成吡喃并[2,3-c]吡唑稠合螺羟吲哚连接的1,2,3-三唑。合成方法涉及一锅，五组分反应使用N-炔丙基拉丁，水合肼,乙酰乙酸乙酯,丙二腈/氰基乙酸乙酯和芳基叠氮化物作为模型底物。机械上,发现反应通过原位吡唑啉酮形成，然后进行Knoevenagel缩合，叠氮炔环加成和迈克尔加成反应。使用基于结构的药物设计开发分子。主要目标是鉴定具有调节α-淀粉酶和DPP4(二肽基肽酶4)活性的潜在能力的抗氧化剂分子。抗氧化剂分析，通过DPPH测定，建议合成的化合物，与丁基化羟基甲苯(BHT)相比,A6和A10具有优异的抗氧化潜能。相比之下,发现化合物A3、A5、A8、A9、A13、A15和A18具有相当的抗氧化潜能。其中,与阿卡波糖相比，A3和A13具有潜在的α-淀粉酶抑制活性，和A3进一步作为具有抗氧化潜力的DPP4和α-淀粉酶的双重抑制剂出现。在其SAR的背景下探索了功能性对其抗氧化剂和酶抑制的关系，并使用计算机技术和酶动力学进一步证实了这一点。
