Antibacterial Evaluation, In Silico Characters and Molecular Docking of Schiff Bases Derived from 5-aminopyrazoles

Ashraf S Hassan; Ahmed A Askar; Eman S Nossier; Ahmed M Naglah; Gaber O Moustafa; Mohamed A Al-Omar

doi:10.3390/molecules24173130

Antibacterial Evaluation, In Silico Characters and Molecular Docking of Schiff Bases Derived from 5-aminopyrazoles

Molecules. 2019 Aug 28;24(17):3130. doi: 10.3390/molecules24173130.

Authors

Ashraf S Hassan¹, Ahmed A Askar², Eman S Nossier³, Ahmed M Naglah^{4

5}, Gaber O Moustafa⁶, Mohamed A Al-Omar⁷

Affiliations

¹ Organometallic and Organometalloid Chemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt. ashraf_salmoon@yahoo.com.
² Botany and Microbiology Department, Faculty of Science (Boys), Al-Azhar University, Cairo 11754, Egypt.
³ Department of Pharmaceutical Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11754, Egypt.
⁴ Department of Pharmaceutical Chemistry, Drug Exploration and Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. anaglah@ksu.edu.sa.
⁵ Peptide Chemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt. anaglah@ksu.edu.sa.
⁶ Peptide Chemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt.
⁷ Department of Pharmaceutical Chemistry, Drug Exploration and Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

Abstract

A series of Schiff bases 14-25 were designed and synthesized for evaluation of their antibacterial properties against multi-drug resistant bacteria (MDRB). The antibacterial activities of Schiff bases 14-25 showed that most of the synthesized compounds displayed a significant antibacterial activity. Assessment of in silico ADMET properties (absorption, distribution, metabolism, excretion and toxicity) of Schiff bases illustrates that all derivatives showed agreement to the Lipinski's rule of five. Further enzymatic assay aided by molecular docking study demonstrated that compound 18 is a potent inhibitor of staphylococcus aureus DNA gyrase and dihydrofolate reductase kinases. This study could be valuable in the discovery of new potent antimicrobial agents.

Keywords: 5-Aminopyrazole; Antibacterial; Dihydrofolate reductase; Molecular docking; Schiff bases; Staphylococcus aureus DNA gyrase.

MeSH terms

Anti-Bacterial Agents / chemical synthesis*
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology
Bacterial Proteins / antagonists & inhibitors
Computer Simulation
DNA Gyrase / metabolism
Folic Acid Antagonists / chemical synthesis
Folic Acid Antagonists / chemistry
Folic Acid Antagonists / pharmacology
Models, Molecular
Molecular Docking Simulation
Molecular Structure
Pyrazoles / chemistry*
Schiff Bases / chemical synthesis*
Schiff Bases / chemistry
Schiff Bases / pharmacology
Staphylococcus aureus / drug effects
Staphylococcus aureus / enzymology*
Tetrahydrofolate Dehydrogenase / metabolism
Topoisomerase II Inhibitors / chemical synthesis
Topoisomerase II Inhibitors / chemistry
Topoisomerase II Inhibitors / pharmacology

Substances

5-aminopyrazole
Anti-Bacterial Agents
Bacterial Proteins
Folic Acid Antagonists
Pyrazoles
Schiff Bases
Topoisomerase II Inhibitors
Tetrahydrofolate Dehydrogenase
DNA Gyrase