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
  • 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.