Laboratorio de Diseño Molecular, Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Ciudad Universitaria, Morelia C.P. 58033, Mexico.
Laboratorio de microRNAs y Cáncer, Universidad Autónoma de Zacatecas, Av. Preparatoria S/N, Agronómica, Campus II, Zacatecas C.P. 98066, Mexico.
Molecules. 2021 Oct 10;26(20):6104. doi: 10.3390/molecules26206104.
A high-order multicomponent reaction involving a six-component reaction to obtain the novel linked 1,5-disubstituted tetrazole-1,2,3-triazole hybrids in low to moderate yield is described. This one-pot reaction is carried out under a cascade process consisting of three sequential reactions: Ugi-azide, bimolecular nucleophilic substitution (S2), and copper-catalyzed alkyne-azide reaction (CuAAC), with high atom and step-economy due the formation of six new bonds (one C-C, four C-N, and one N-N). Thus, the protocol developed offers operational simplicity, mild reaction conditions, and structural diversity. Finally, to evaluate the antitumoral potential of the synthetized molecules, a proliferation study was performed in the breast cancer (BC) derived cell line MCF-7. The hybrid compounds showed several degrees of cell proliferation inhibition with a remarkable effect in those compounds with cyclohexane and halogens in their structures. These compounds represent potential drug candidates for breast cancer treatment. However, additionally assays are needed to elucidate their complete effect over the cellular hallmarks of cancer.
描述了一种涉及六组分反应的高阶多组分反应，以低至中等产率获得新型连接的 1,5-取代的四唑-1,2,3-三唑杂合体。该一锅反应在由三个连续反应组成的级联过程中进行：Ugi-叠氮化物、双分子亲核取代（S2）和铜催化的炔烃-叠氮化物反应（CuAAC），由于形成六个新键（一个 C-C、四个 C-N 和一个 N-N），因此具有高原子经济性和步骤经济性。因此，所开发的方案提供了操作简单、反应条件温和和结构多样性。最后，为了评估合成分子的抗肿瘤潜力，在乳腺癌（BC）衍生的细胞系 MCF-7 中进行了增殖研究。杂合体化合物表现出不同程度的细胞增殖抑制，其中那些结构中具有环己烷和卤素的化合物具有显著的效果。这些化合物代表了用于乳腺癌治疗的潜在药物候选物。然而，需要进一步的试验来阐明它们对癌症细胞特征的全面影响。
