Synthesis, enzyme inhibition, and docking studies of new schiff bases of disalicylic acid methylene-based derivatives as dual-target antibacterial agents

Abstract

The findings showed that <b>6a-l</b> have significant antibacterial activity against both Gram-positive and Gram-negative bacteria, with inhibition zones (IZ) comparable to or even higher than the reference Ciprofloxacin. MIC testing revealed that <b>6h</b> and <b>6l</b> were 1.5 times as effective than ciprofloxacin against <i>S. aureus</i>. Compounds <b>6h</b> and <b>6l</b> had MBC values of 28 and 33 nM for <i>S. aureus</i>, compared to Ciprofloxacin's 45 nM, indicating that they are more potent bactericidal agents. The MIC values for compounds <b>6c</b>, <b>6e</b>, <b>6h</b>, <b>6j</b>, and <b>6l</b> against <i>A. flavus</i> were between 14.50 and 19.50 µM, while the MIC value for fluconazole was 11.50 µM. Also, the studied compounds had MIC values between 18.20 and 22.90 µM against <i>C. albicans</i>, while Fluconazole had a MIC value of 17.50 µM. Compound <b>6h</b> showed a MIC value of 1.70 µM against the clinical strain <i>S. aureus</i> (ATCC 43300) (MRSA), making it an effective antibacterial agent. Compounds <b>6h</b>, <b>6j</b>, and <b>6l</b> inhibited <i>E. coli</i> DNA gyrase with IC₅₀ values of 79, 117, and 87 nM, respectively, compared to the reference novobiocin (IC₅₀ = 170 nM). Additionally, compounds <b>6h</b> and <b>6l</b>, the most potent <i>E. coli</i> gyrase inhibitors, showed encouraging results on DHFR. Compounds <b>6h</b> and <b>6l</b> exhibit IC₅₀ values of 3.80 µM and 4.25 µM, respectively. These values are significantly lower and hence more effective than Trimethoprim's IC₅₀ of 5.20 µM.