Styryl carbamate backbones for the discovery of TME-disrupting agents

Abstract

Twenty-one styryl carbamates have been designed, synthetized and characterized by their physical properties. Afterwards, their potential activity as tumor microenvironment disruptors has been evaluated. First, antiproliferative studies on tumor cell lines HT-29, A-549 and MCF-7 and on non-tumor cell line HEK-293 were carried out. Then, the antiproliferative activity of some selected compounds was evaluated on co-cultures of A-549 and immune cells, Jurkat T or monocytes THP-1. To determine their potential as oncoinflammation regulators, the secretion levels of IL-6, TNF-α and SAA-1 were, also, determined from these co-culture assays. Then, the effect on the expression levels of anticancer targets PD-L1 in both A-549 and monocytes THP-1 were established and, finally, the expression of CD80 and CD11b in THP-1. Compounds 9–13 bearing halophenyl carbamate units exhibited promising results as TME disruptors and inflammation regulators.