Synthesis of 2-aminothiazole sulfonamides as potent biological agents: Synthesis, structural investigations and docking studies.

A simplified synthetic approach involving sulfonylation followed by amino group alkylation produced new 2-aminothiazole derivatives. UV/Vis, infrared, and NMR spectroscopies confirmed their structures. Compounds , , , and showed strong inhibition against Jack bean and Bacillus Pasteurii urease, with IC values from 14.06 to 20.21 μM/mL. Compounds , , , , , , and exhibited potent inhibitory effects against α-glucosidase and α-amylase, with IC values between 20.34 and 37.20 μM/mL. Compounds , , and demonstrated potent DPPH scavenging, with IC values around 34.4-39.2 μM/mL. FMO analysis showed compounds , , , and having parallel aromatic ring systems due to π cloud interactions, while compounds and had distinct electronic density distributions. Compound had HOMO and LUMO energy gaps of 5.805 eV, with bromo and fluoro substitutions in compounds and slightly increasing the gaps to 6.089 eV and 6.078 eV, respectively. Nitro groups in compounds and reduced the gaps to 0.384 eV and 1.187 eV. All compounds demonstrated high gastrointestinal absorption, non-permeability to the blood-brain barrier, and optimal skin permeation (Log Kp between -5.83 and -6.54 cm/s). Compounds , , and had promising QED scores of 0.719, 0.707, and 0.860, respectively, with synthetic accessibility scores from 2.057 to 2.517. ADMET predictions indicated minimal toxicity, cardiovascular safety, and significant inhibitory potential for CYP enzymes. Strong in silico binding affinities (binding energies -5.75 to -7.63 kcal/mol) and metabolic stability suggest these derivatives are promising candidates for further drug development.