1,2,3-Triazole Tethered 2-Mercaptobenzimidazole Derivatives: Design, Synthesis and Molecular Assessment Toward C6 Glioma Cell Line
Peterson de Andrade, Amanda de Fraga Dias, Fabrício Figueiró, Fernando Torres, Daniel Fábio Kawano, Ana Maria Oliveira Battastini, Ivone Carvalho, Carlos Henrique Tomich de Paula da Silva, Joaquín M. Campos Rosa
Abstract
Aim: Glioblastoma multiforme (GBM) is an aggressive cancer with very limited clinical therapies. Herein, we have designed novel mercaptobenzimidazole derivatives (1–7) as multitarget antineoplastic drugs and assessed their antiproliferative profiles on an experimental model for GBM, the C6 glioma line. Results: The target compounds were synthesized in few steps with reasonable yields (33–90%). Compounds 1 (∼18 μM) and 4 (∼20 μM) showed dose-dependent antiproliferative effects on C6 glioma and significantly increased early apoptosis, but only 4 disrupted the cell cycle progression and did not induce autophagy. Docking simulations suggested these compounds as dual kinase and colchicine binding site inhibitors. Conclusion: In spite of the limited selective toxicity, 4 hold the potential to be further optimized for the treatment of GBM.