Synthesis, Enzyme Inhibition, and Docking Studies of New Schiff Bases of Disalicylic Acid Methylene-based Derivatives As Dual-target Antibacterial Agents

Overview

Journal Front Chem

Specialty Chemistry

Date 2024 Nov 27

PMID 39600312

Authors

Lamya H Al-Wahaibi

Mohamed A Mahmoud

Hayat Ali Alzahrani

Hesham A Abou-Zied

Alshaimaa Abdelmoez

Bahaa G M Youssif

Stefan Brase

Safwat M Rabea

Affiliations

Soon will be listed here.

Abstract

Introduction: Bacteria have acquired resistance to almost all antibiotics currently in use due to their extensive, broad, and improper utilization over a prolonged period. DNA gyrase and DHFR exhibit significant promise as targets for antibacterial therapeutics.

Methods: We have developed a series of disalicylic acid methylene/Schiff bases hybrids () that function as antibacterial agents by targeting DNA gyrase and DHFR.

Results And Discussion: The findings showed that 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 and were 1.5 times as effective than ciprofloxacin against . Compounds and had MBC values of 28 and 33 nM for , compared to Ciprofloxacin's 45 nM, indicating that they are more potent bactericidal agents. The MIC values for compounds , , , , and against 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 , while Fluconazole had a MIC value of 17.50 µM. Compound showed a MIC value of 1.70 µM against the clinical strain (ATCC 43300) (MRSA), making it an effective antibacterial agent. Compounds , , and inhibited DNA gyrase with IC values of 79, 117, and 87 nM, respectively, compared to the reference novobiocin (IC = 170 nM). Additionally, compounds and , the most potent gyrase inhibitors, showed encouraging results on DHFR. Compounds and exhibit IC values of 3.80 µM and 4.25 µM, respectively. These values are significantly lower and hence more effective than Trimethoprim's IC of 5.20 µM.

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