Comparative Evaluation of the Antibacterial and Pharmacokinetic Activities of Curcumin and its Schiff Base Derivatives Against E. coli: Experimental and Theoretical Studies.

Abstract

Systematic structural modification of curcumin can generate novel analogues with 
improved biological and pharmacological properties. In this study, Schiff base 
derivatives of curcumin were synthesized via condensation reactions with isoniazid 
and 2-furoic hydrazide. The resulting compounds were characterized using CHN 
elemental analysis, infrared (IR) spectroscopy, and nuclear magnetic resonance 
(NMR) spectroscopy to confirm their structural integrity. Further structural 
elucidation and electronic property evaluation were performed using quantum 
chemical calculations based on Density Functional Theory (DFT). 
The electronic structures of the synthesized derivatives were optimized at the 
B3LYP/6-311+G(d,p) level of theory. The DFT results revealed that the modified 
compounds exhibit enhanced chemical reactivity relative to native curcumin, as 
indicated by a reduced HOMO–LUMO energy gap and an increased electrophilicity 
index. These electronic parameters suggest improved interaction potential with 
biological targets. Comparative in vitro antibacterial assays demonstrated that the 
synthesized derivatives exhibit superior inhibitory activity against Escherichia coli 
compared with unmodified curcumin. Complementary in silico molecular docking 
studies further supported these observations, showing stronger binding affinities of 
the derivatives toward the E. coli target protein (PDB ID: 6F86). Pharmacokinetic 
and toxicity assessments based on ADMET predictions indicated improved intestinal 
absorption for the synthesized derivatives, whereas curcumin exhibited relatively 
better tissue distribution characteristics. Importantly, the derivatives were 
predicted to possess low toxicity and were classified as non-hepatotoxic, consistent 
with the safety profile of curcumin. Overall, the findings highlight the potential of 
curcumin-derived Schiff bases, particularly the isoniazid-based analogue, as 
promising antibacterial agents with enhanced biological activity and favorable 
pharmacokinetic properties.