Benzothiazoles, an anticonvulsant, antiviral, antihypertensive, and cancer-fighting medication of the heterocyclic scaffold family, also acts as antibacterial and antiviral agents. There is much interest in this chemical’s production because of the strong and vital biological action it possesses. Substituted aromatic aldehydes were combined with 2-amino-benzothiazole-6-sulfonic acid amides, or Schiff base derivatives, to create Schiff base derivatives. Recrystallized, characterized, and tested for diuretic efficacy in vivo using online tools, m.p. (melting point), Rf, FTIR (Fourier transform infrared), 1H-NMR (proton nuclear magnetic resonance) data The molecular characteristics of all the substances created were estimated using Lipinski’s rule of 5, OSIRIS (software) molecular property explorer, Molsoft, and Autodock 4.0 docking software. Male Wistar rats were used to make all the compounds traditionally in order to test for diuretic activity. Neither the elemental nor the spectral information for the synthesized compounds disagreed. There were five different methods used to evaluate these compounds: Lipinski rule of five, Molsoft to determine molecular characteristics, PASS (prediction of activity spectra for substances) values to determine the diuretic effect, and OSIRIS software to determine toxicology. In order to investigate the diuretic effects of the selected drugs, docking analysis was used. Acetazolamide was shown to have a diuretic effect that was superior to that of compounds IIIb and IIIe, whereas 2-{(E)-[(3-hydroxyphenyl)methylidene]amino}-1,3-benzothiazole-6-sulfonamide (IIIb) was found to be the most promising potential.