Structural and antimicrobial activity studies of brand new benzothiazole-pyrazole conjugates.

• Seven benzothiazole-pyrazole conjugates were synthesized and characterized by IR, NMR, and MASS analyses. • The DFT studies of the synthesized aminopyrazolyl benzothiazole analogues presented angular conformations. • The phenylpyrazole benzothiazole conjugates 8 – 10 exhibited lower HOMO-LUMO gap (ΔE H-L) than others (3.61–4.39 eV). • Both conjugates 8 and 10 demonstrated significant antibacterial activity, especially against S. aureus. • Conjugate 10 displayed the highest binding affinity, indicating a very strong interaction with the PDB: 4DUH. The targeted benzothiazole-pyrazole conjugates 4, 6, 8, 9 , and 10 were synthesized through introducing the pyrazole moiety to the precursor 2-acetamido-6-(2-cyanoacetyl) benzothiazole (3). The structure of isolated conjugates was elucidated using FT-IR, 1H/13C NMR, and mass spectral techniques, as well as elemental analyses (C, H, and N). The DFT/B3LYP methodology revealed that the isolated conjugates had an angular configuration. Meanwhile, the antimicrobial efficiency of the benzothiazole-pyrazole conjugates have been assessed against several bacterial and fungal strains. Conjugate 8 exhibited remarkable and broad-spectrum activity toward S. aureus and A. fumigatus (MIC < 37 and < 226 µg/mL, respectively). Conjugate 10 was very effective against K. pneumoniae and A. fumigatus (MIC < 42 and < 219 µg/mL), implying its potential as a versatile antimicrobial agent. Furthermore, the new conjugates have the ability to inhibit DNA gyrase; conjugates 4b, 8, 9 , and 10 exhibited comparable inhibitory effects, while conjugates 6a and 6b displayed slightly less potent inhibitory action. Moreover, molecular docking simulations have been carried out to investigate the interactions of novel benzothiazole-pyrazole conjugates with PDB: 4DUH protein. Also, SwissADME analysis was utilized to assess the pharmacokinetic characteristics of the synthesized conjugates. This research offers a comprehensive understanding of the drug-like characteristics and pharmacokinetic features of the benzothiazole-pyrazole conjugates. [Display omitted] [ABSTRACT FROM AUTHOR]