New Hybrids with 2-aminobenzothiazole and Azelayl Scaffolds: Synthesis, Molecular Docking and Biological Evaluation

Novel compounds containing both benzothiazole and azelayl scaffolds were synthesized through Schotten Baumann type reaction between azelayl chloride methyl ester and a series of 2-aminobenzothiazole derivatives bearing different substituents on the aromatic carbocyclic ring. The design of the new hybrids was inspired by their analogy with the structure of some HDAC inhibitors, such as Vorinostat and 9-hydroxystearic acid. Molecular docking on some compounds predicted an activity as inhibitors of HDAC, and this prediction was confirmed by in vitro essays on a human colon cancer cells line (HT 29). The antimicrobial activity against some representative human pathogens and several Lactobacillus and Bifidobacterium strains isolated from human microbiotas was also evaluated. The new hybrids showed antiproliferative activity on cancer cells while no antimicrobial activity was observed in the range of concentrations used for cancer cells and this finding might represent an important tool in the fight against cancer minimizing some side effects on the microbiotas typical of an anticancer treatment.