Novel arylazothiazoles and arylazo[1,3,4]thiadiazoles as potential antimicrobial and anticancer agents: synthesis, molecular modeling, and biological screening

In this study, we tested two novel series of 5-arylazo-2-hydrazonothiazoles 6a-g and 2-hydrazono[1,3,4]thiadiazoles 12a-c as antimicrobial and anticancer agents. These series were prepared from the reactions of 2-{1-[4-(2,4-dihydroxyphenylazo)phenyl]ethylidene}thiosemi-carbazide (3) with alpha-keto hydrazonoyl halides and N-aryl arenecarbohydrazonoyl halides. The structures of the newly synthesized compounds were elucidated by infrared, H-1 and C-13 nuclear magnetic resonance, and gas chromatography mass spectrometry spectral data. The antibacterial activity against two types of Gm +ve bacteria and, two types for Gm -ve bacteria, and the antifungal activity against four fungi microorganisms were evaluated by a well diffusion method for the synthesized compounds. Of these novel compounds, thiazole derivatives 6a-g showed mostly promising antibacterial activity against Gm +ve strains and antifungal activity compared to the reference drugs. A successful step was achieved to explain of their mode of action through molecular docking of the most active molecules at a target enzyme, CYP51. Moreover, the antiproliferative activity was tested against three human carcinoma cell lines [human colon carcinoma (HCT-116), human breast adenocarcinoma (MCF-7), and human liver carcinoma (HEPG-2)], showing promising anticancer activities compared to the doxorubicin drug. The data suggest that the arylthiazole scaffold derivatives 6a-g exhibited good antimicrobial and anticancer activities and might be used as leads for further optimization.