Design, Synthesis, and Biological Evaluations of Novel Azothiazoles Based on Thioamide

Abstract

Herein we studied the preparation of different thiazoles via the reaction of 2-(3,4-dimethoxybenzylidene)hydrazine-1-carbothioamide (1) with hydrazonoyl halides under base-catalyzed conditions. The reactions proceed through nucleophilic substitution attack at the halogen atom of the hydrazonoyl halides by the thiol nucleophile to form an S-alkylated intermediate. The latter intermediate undergoes cyclization by the loss of water to afford the final products. The structures of the azo compounds were confirmed by FTIR, MS, NMR, and elemental analyses. Indeed, the newly synthesized azo compounds were estimated for their potential anticancer activities by an MTT assay against different human cancer cells, such as lung adenocarcinoma (A549) and colorectal adenocarcinoma (DLD-1). The caspase-3 levels were also estimated using Western blotting and the dual staining technique to evaluate the potency of the titled compounds to promote apoptosis.

Keywords: anticancer activities; carbothioamide; hydrazonoyl; thiazole.

Scheme 1

Synthesis of monoazothiazoles 8–13.

Scheme 2

Synthesis of bisazothiazoles 17–19.

Figure 1

The levels of Caspase-3 in A5941 and DLD-1 cells of various groups were examined by Western blotting.

Figure 1

The levels of Caspase-3 in A5941 and DLD-1 cells of various groups were examined by Western blotting.

Figure 2

(a) dual staining of A549 cells via the fluorescent homidium bromide and acridine orange dyes; (b) apoptosis in fold.

Figure 3

(a) dual staining of DLD-1cells via the fluorescent homidium bromide and acridine orange dyes; (b) apoptosis in fold.