Synthesis, Computational, and UV-Vis Absorption Studies of Novel Benzothiazole Azo Derivatives and Their Biological Potentials

Objective: In the present work, a series of novel mono-azo benzothiazole derivatives were synthesized via the diazo-coupling reaction of cyclopentane-1,3-dione with various substituted benzothiazole amines. The synthesized compounds were thoroughly characterized, and their biological potential was evaluated by testing their antitubercular and antimicrobial activities. Methods: The target compounds were synthesized through a diazo-coupling reaction of different benzothiazole amines with cyclopentane-1,3-dione. Computational studies were performed using the DFT/B3LYP method with the 6-31G++(d,p) basis set. Additionally, in silico molecular docking studies of the target compounds were conducted with the enoyl-ACP reductase receptor. Results and Discussion: The structures of the target azo compounds were confirmed by various spectroscopic techniques, including FT-IR, NMR (¹H and ¹³C), and HRMS. Quantum chemical parameters, frontier molecular orbitals, and molecular electrostatic potential surfaces were evaluated using DFT to elucidate the electronic properties of the benzothiazole azo dyes. The UV-Vis absorption studies of the synthesized compounds were conducted in 6 organic solvents. The target azo dyes were screened for their antitubercular activity against the M. tuberculosis H37Rv strain. The antibacterial activity of the target compounds was tested against four bacterial pathogens (S. aureus, S. mutans, E. coli, and S. typhi), and their antifungal activity was evaluated against the fungal strain A. niger. Conclusions: Antitubercular activity results revealed that the compound 3-hydroxy-2-{[4-methylbenzo(d)thiazol-2-yl]diazinyl}cyclopent-2-en-1-one displayed promising activity with a minimal inhibitory concentration of 3.25 µg/mL compared to the other synthesized compounds. In antimicrobial activity, the compounds 2-[benzo(d)thiazol-2-yl]diazenyl-3-hydroxycyclopent-2-en-1-one, 3-hydroxy-2-{[4-methylbenzo(d)thiazol-2-yl]diazinyl}cyclopent-2-en-1-one, and 3-hydroxy-2-{[6-methylbenzo(d)thiazol-2-yl]diazinyl}cyclopent-2-en-1-one exhibited significant activity against the tested pathogens. Furthermore, docking results suggested that the target compounds displayed favorable docking scores and showed significant binding interactions with amino acid residues.