Department of Organic Chemistry, Instituto de Química, UNAM, Circuito Exterior S.N., Ciudad Universitaria, Coyoacán, México, DF 04510, Mexico.
Department of Organic Chemistry, Instituto de Química, UNAM, Circuito Exterior S.N., Ciudad Universitaria, Coyoacán, México, DF 04510, Mexico.
Bioorg Med Chem Lett. 2021 May 15;40:127899. doi: 10.1016/j.bmcl.2021.127899. Epub 2021 Mar 13.
We report a practical two-step approach involving a Ugi 4-CR/ azide-alkyne cycloaddition for the synthesis of biaryl-containing cyclophanes. The series represents an extension of our previously reported macrocycles as an effort to enhance the anti-proliferative activity of this scaffold. In this variant, we incorporate a biphenyl moiety in the framework, thus enhancing the macrocycle size, lipophilicity, and structural diversity. Macrocycles were tested against different cell lines, being more cytotoxic against prostate (PC-3 and DU-145) and breast (MCF-7) tumor cells. Gratifyingly, the most active compound showed a significative enhancement of PC-3 growth inhibition with respect to our previous series, reaffirming the potential anti-proliferative activity of this kind of cyclophanes.
我们报告了一种实用的两步法，涉及 Ugi 4-CR/叠氮化物-炔烃环加成反应，用于合成含联苯的环芳烃。该系列是我们之前报道的大环的扩展，旨在增强该支架的抗增殖活性。在这种变体中，我们在框架中引入联苯部分，从而增加了大环的尺寸、亲脂性和结构多样性。大环化合物针对不同的细胞系进行了测试，对前列腺（PC-3 和 DU-145）和乳腺（MCF-7）肿瘤细胞的细胞毒性更强。令人高兴的是，最活跃的化合物对 PC-3 的生长抑制作用明显增强，与我们之前的系列相比，这再次证实了这种环芳烃的潜在抗增殖活性。
