Synthesis, Spectral Characterization, Antibacterial Evaluation and Pharmacophore Analysis of Novel 1,3,4-Thiadiazole-Indole Schiff Bases
TL;DR
Overall, structural modification of the Schiff-base aryl moiety influenced both antibacterial activity and pharmacophoric characteristics, with compound 1H identified as the most promising candidate for further optimization.
Abstract
A series of novel Schiff bases (1A–1I) was synthesized from 5-(1H-indol-2-yl)-1,3,4-thiadiazol-2-amine (ITA) through condensation with substituted aromatic aldehydes and acetophenones under reflux conditions. The synthesized compounds were characterized by melting point, FT-IR, 1H NMR, and EI-MS analyses. Formation of the Schiff bases was confirmed by the characteristic C=N stretching absorption at 1611–1636 cm⁻¹. Among the synthesized derivatives, the 2-chlorophenyl analogue 1H exhibited the most promising antibacterial activity, particularly against E. coli and S. typhi, whereas compounds 1B and 1D showed comparatively better activity against Gram-positive bacteria. Compound 1E also demonstrated notable activity against Gram-negative strains. Pharmacophore modelling following MMFF94 minimization revealed important hydrophobic/lipophilic, hydrogen-bond donor, and hydrogen-bond acceptor features. Overall, structural modification of the Schiff-base aryl moiety influenced both antibacterial activity and pharmacophoric characteristics, with compound 1H identified as the most promising candidate for further optimization.