Synthesis and Biochemical Studies of Novel Mon-Azothiazoles and Bis-Azothiazoles Based on 2-(4-(Dimethylamino)Benzylidene)Hydrazine-1-Carbothioamide

Abstract

The present research describes the preparation of novel mon-azothiazoles and bis-azothiazoles based on hydrazonoyl halides. These thiazoles are prepared from the reaction of 2-(4-(dimethylamino)benzylidene)hydrazine-1-carbothioamide with α-haloketohydrazonoyl halides in the basic medium (triethylamine) at reflux. The process of preparation is designed and illustrated in the manuscript. The mechanism of the final novel mono- and bis-azothiazoles can be described through thiol group of 2-(4-(dimethylamino)benzylidene)-hydrazine-1-carbothioamide undergo nucleophilic attack to carbon attached to halogen from hydrazonoyl to form S-alkylated intermediate. The intermediate is eliminated hydrogen chloride then at once undergoes intramolecular cycloaddition followed by exclusion of water to provide the novel series of mono- and bis-azothiazole. Structures of the final products were elucidated by FTIR, MS, NMR and elemental analyses. These reactions are provided the desired products in excellent yields. The antiproliferation activity of the newly synthesized compounds was evaluated using the MTT assay against human colorectal adenocarcinoma (DLD-1) and human adenocarcinoma (A549) cells. Furthermore, apoptosis induction was also investigated via the estimation of the caspase-3 levels using western blotting and dual staining technique.

Keywords:

• Hydrazonoyl
• thiazole
• carbothioamide
• antiproliferation activity
• apoptosis induction

Acknowledgment

This work was supported by “the Deanship of Scientific Research, Vice Presidency for Graduate Studies and Scientific Research, King Faisal University, Saudi Arabia [Project No. GRANT311]”.

Disclosure statement

No potential conflict of interest was reported by the authors.