Design, synthesis and molecular modeling of isatin-aminobenzoic acid hybrids as antibacterial and antibiofilm agents

Number of factors, including newly emerging infectious diseases and an increase in multi-drug resistant microbial pathogens with particular relevance for Gram-positive bacteria, make the treatment of infectious diseases in hospital-based healthcare a major challenge in the medical community. 4-Amino...

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Bibliographic Details
Published in:	Saudi pharmaceutical journal Vol. 31; no. 11; p. 101781
Main Authors:	Radwan, Awwad A., Al-Anazi, Fares K., Al-Agamy, Mohammed, Alghaith, Adel F., Mahrous, Gamal M., Alhuzani, Mohammad R., Alghamdi, Abdulrhman S.A.
Format:	Journal Article
Language:	English
Published:	Elsevier B.V 01-11-2023 Elsevier
Subjects:	Aminobenzoic acid Antibacterial activity Docking study Original Schiff’s bases Synthesis Aminobenzoic acid Antibacterial activity Schiff’s bases Docking study Synthesis
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Summary:	Number of factors, including newly emerging infectious diseases and an increase in multi-drug resistant microbial pathogens with particular relevance for Gram-positive bacteria, make the treatment of infectious diseases in hospital-based healthcare a major challenge in the medical community. 4-Aminobenzoic acid (PABA), has demonstrated a variety of biological actions particularly, antimicrobial activity. In our study we coupled this vitamin-like molecule with different isatin derivatives. We investigated the antibacterial activity of the synthesized Schiff's bases. The compounds showed high selective activity against Gram-positive bacteria and showed weak or no activity against both Gram-negative bacteria and fungi. Compound 2a showed highest activity against S. aureus and B. subtilis (MIC 0.09 mmol/L). Additionally, these substances exhibit strong anti-B. Subtilis biofilm formation. We were able to shed insight on the binding mode of these new inhibitors using in silico docking of the compounds in the binding sites of a 3D structure of B. subtilis histidine kinase/Walk. The binding free energy of the compound 2a to the catalytic domain walk, of histidine kinase enzyme of B. subtilis bacteria, was calculated using molecular mechanics/generalized born surface area scoring. The key residues for macromolecule–ligand binding were postulated. The optimized 3D protein–ligand binding modes shed light on the B. subtilis HK/Walk–ligand interactions that afford a means to assess binding affinity to design new HK/Walk inhibitor as antibacterial agents.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1319-0164 2213-7475
DOI:	10.1016/j.jsps.2023.101781