A Novel of Azo-Thiazole Moiety Alternative for Benzidine-Based Pigments: Design, Synthesis, Characterization, Biological Evaluation, and Molecular Docking Study

Abstract

A new series of coloring compounds (pigments) based on 5-(2-aminothiazol-5-yl)thiazol-2-amine and 5-(4-aminophenyl)thiazol-2-amine as heterocyclic alternatives for benzidine based on disazo dyestuffs were synthesized. All the newly synthesized pigments are characterized based on their physical, spectral, and analytical data. The antimicrobial activity showed that introducing the heterocyclic analogues thiazole (mono or bis) exhibited less toxic and resisted antimicrobial (five gram-positive strain, three gram-negative, and three fungal species). Thus, derivatives demonstrated moderate to good activity compared with Gentamycin and Ketoconazole. Furthermore, the pigments screened for their in vitro antioxidant properties by the DPPH method, and the newly designed pigments PG4–PG11 with thiazole moiety causes increase antioxidant properties with IC₅₀ values ranged between (0.054–0.192 µM) compared with PG1, PG2, and PG3 (IC₅₀ = 0.712, 0.239, and 0.191 µM) as well as Ascorbic acid (IC₅₀ = 2.532 µM). Further, the synthesized pigments' cytotoxicity activity evaluated against HepG-2 and showed IC₅₀ values ranged between (53.52–94.05 µM) compared with PG1–PG3 (IC₅₀ =216.04–393.58 µM) and doxorubicin (IC₅₀ = 8.17 µM). Molecular docking study concluded that thiazole moiety might be made one or more binding mode as critical hydrogen bonding through the nitrogen of thiazole, as well as arene-cation and/or arene-arene interaction with dihydrofolate reductase (DHFR) active site in 1DLS protein.

Keywords:

• Benzidine pigments analogue
• cytotoxicity
• skin antimicrobial
• antioxidant
• molecular docking

Disclosure statement

No potential conflict of interest was reported by the authors.

Dedication

All authors want to dedicate this work to Prof. Dr. Mohamed A. El-Borai professor of organic chemistry-Chemistry department, Faculty of Science, Tanta University, who passed away while reviewing the research, wishing God to bless him in his mercy, dwell in his paradise, and inspire his family patience and solace. Additionally, we are sorry for his loss. He was such a great person; He will live on in our memories forever.