Synthesis of G-quadruplex-targeting flexible macrocyclic molecules via click reaction

Abstract

Four flexible macrocycles, such as cTz (1), cTN (2), cPT (3), and cPTN (4), were efficiently synthesized through cyclodimerizing triazo-alkynyl-containing monomers via Cu(I)-catalyzed click reactions with optimized conditions. The starting materials were pyrrole and triazole derivatives containing amine and carboxyl groups, followed by amide coupling to introduce the triazo and alkynyl groups to prepare the cyclization precursors. The electrospray ionization mass spectrometry (ESI-MS) results indicated that cTN (2) and cPT (3) showed the ability to bind with c-myb G-quadruplex. Therefore, cTN (2) and cPT (3) molecules might be potential leading compounds for anti-cancer drug discovery.