Combretastatin A-4 sulfur-containing heterocyclic derivatives: Synthesis, antiproliferative activities and molecular docking studies

Abstract

Combretastatin A-4 inspired heterocyclic derivatives were synthesized and evaluated for their biological activities on tubulin polymerization and cell proliferation. Among the 19 described sulfur-containing compounds, derivatives (Z)-4h and (Z)-4j exhibited interesting in cellulo tubulin polymerization inhibition and antiproliferative activities with IC₅₀ values for six different cell lines between 8 and 27 nM. Furthermore, in silico docking studies within the colchicine/CA-4 binding site of tubulin were carried out to understand the interactions of our products with the protein target. The effects on the cell cycle of follicular lymphoma cells were also investigated at 1-10 nM concentrations showing that apoptotic processes occurred.

Keywords: Antiproliferative agents; Cancer; Combretastatin A-4; Heterocycles; Inhibitors of tubulin assembly.