Li Xiang, Li Xue-Qiang, Liu He-Mei, Zhou Xue-Zhang, Shao Zhi-Hui
Key Laboratory of Energy Sources & Chemical Engineering, Development Center of Natural Products and Medication and School of Chemistry and Chemical Engineering, Ningxia University, Yinchuan, 750021, China.
Org Med Chem Lett. 2012 Jul 3;2(1):26. doi: 10.1186/2191-2858-2-26.
1,2,4-Triazole derivatives have received much attention due to their versatile biological properties including antibacterial, antifungal, anticonvulsant, antiinflammatory, anticancer, and antiproliferative properties. 1,2,4-Triazole nucleus has been incorporated into a wide variety of therapeutically interesting molecules to transform them into better drugs. Schiff bases of 1,2,4-triazoles have also been found to possess extensive biological activities. On the other hand, γ-substituted butenolide moiety represents a biological important entity that is present in numerous biologically active natural products.
We have described herein the synthesis of 12 hybrid 1,2,4-triazole Schiff bases bearing γ-substituted butenolide moiety. These compounds were synthesized by utilizing the tandem asymmetric Michael addition/elimination reaction as the key step. All the new compounds were evaluated for their in vitro anticancer activity.
Tandem asymmetric Michael addition/elimination approach has offered an easy access to new chiral 1,2,4-triazole compounds 7a-7l. All these chiral 1,2,4-triazole derivatives exhibited good anticancer activities towards Hela. Of all the tested compounds, the chiral compound 7l with an IC50 of 1.8 μM was found to be the most active.
1,2,4-三唑衍生物因其多样的生物学特性，包括抗菌、抗真菌、抗惊厥、抗炎、抗癌和抗增殖特性而备受关注。1,2,4-三唑核已被引入到各种各样具有治疗意义的分子中，以将它们转化为更好的药物。1,2,4-三唑的席夫碱也被发现具有广泛的生物活性。另一方面，γ-取代丁烯内酯部分是一种生物学上重要的实体，存在于许多生物活性天然产物中。
本文描述了12种带有γ-取代丁烯内酯部分的杂化1,2,4-三唑席夫碱的合成。这些化合物通过串联不对称迈克尔加成/消除反应作为关键步骤合成。所有新化合物均进行了体外抗癌活性评估。
串联不对称迈克尔加成/消除方法为新型手性1,2,4-三唑化合物7a - 7l的合成提供了一条简便途径。所有这些手性1,2,4-三唑衍生物对Hela细胞均表现出良好的抗癌活性。在所有测试化合物中，IC50为1.8 μM的手性化合物7l被发现是活性最高的。
