DESIGN AND BIOLOGICAL PROFILING OF A NOVEL (2,4-BIS(ARYLAMINO) THIAZOL-5-YL) (THIOPHEN-2-YL) METHANONE DERIVATIVE: IMPACT OF SUBSTITUENT VARIATIONS

A series of novel (2,4-bis(arylamino) thiazol-5-yl) (thiophen-2-yl) methanone derivatives were synthesized and analyzed using various analytical and spectral techniques, including elemental analysis, IR spectroscopy, ¹H NMR, ¹³C NMR, and mass spectrometry to ensure comprehensive structural validation and accurate determination of their chemical composition and framework. Structural optimization and theoretical vibrational spectral interpretations were performed using density functional theory (DFT) calculations. The study examined critical molecular properties, such as charge transfer phenomena, chemical stability, HOMO-LUMO energy gaps, Natural Bond Orbital (NBO) analysis, Molecular Electrostatic Potential (MEP) mapping, and Non-linear Optical (NLO) properties. Biological testing indicated that all synthesized compounds exhibited significant antibacterial activity. Among these, (4-((4-chlorophenyl) amino)-2-(4-ethoxyphenyl) amino) thiazol-5-yl) (thiophen-2-yl) methanone emerged as the most potent antibacterial agent. Molecular docking studies were conducted with the 3IP4 and 1KEB receptor proteins, shedding light on the potential binding interactions and underlying mechanisms. This comprehensive study showcases the synthesis, theoretical evaluation, and biological potential of these thiazole-based derivatives, highlighting their promise as candidates for developing effective antibacterial agents.