2. Academic Validation
  3. Multicomponent synthesis and anti-proliferative screening of biaryl triazole-containing cyclophanes

Multicomponent synthesis and anti-proliferative screening of biaryl triazole-containing cyclophanes

  • Bioorg Med Chem Lett. 2021 May 15:40:127899. doi: 10.1016/j.bmcl.2021.127899.
Eduardo Hernández-Vázquez 1,  Yoarhy A Amador-Sánchez 2,  Marco A Cruz-Mendoza 2,  María T Ramírez-Apán 2,  Luis D Miranda 3
Affiliations

Affiliations

  • 1 Department of Organic Chemistry, Instituto de Química, UNAM, Circuito Exterior S.N., Ciudad Universitaria, Coyoacán, México, DF 04510, Mexico. Electronic address: [email protected].
  • 2 Department of Organic Chemistry, Instituto de Química, UNAM, Circuito Exterior S.N., Ciudad Universitaria, Coyoacán, México, DF 04510, Mexico.
  • 3 Department of Organic Chemistry, Instituto de Química, UNAM, Circuito Exterior S.N., Ciudad Universitaria, Coyoacán, México, DF 04510, Mexico. Electronic address: [email protected].
PMID: 33722739 DOI: 10.1016/j.bmcl.2021.127899
Abstract

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.

Keywords

Anti-proliferative activity; Cyclophanes; Multicomponent synthesis; PC-3 cell line.

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