Synthesis, spectral characterization of pyrazole derived Schiff base analogs: molecular dynamic simulation, antibacterial and DNA binding studies

Abstract

We have synthesized the pyrazole-bearing Schiff base derivatives (5a–5e) and (6a–6h) then the structural confirmation was supported by various spectral analyses. The antibacterial activity of all analogs was screened against bacterial strains Staphylococcus aureus, Bacillus subtilis, Enterococcus faecalis, Escherichia coli, Klebsiella pneumonieae and Pseudomonas aeruginosa. In comparison to the reference drug ciprofloxacin, the lead analogs 5c and 6c showed potent activity, with MIC values of 64 µg/mL against E. coli and B. subtilis. Compound 5c showed a moderate effect with a MIC value of 128 µg/mL against B. subtilis, P. aeruginosa and K. pneumonieae, while compound 6c was against E. coli and P. aeruginosa. Furthermore, the compounds 5c and 6c displayed groove binding mode towards CT-DNA by absorption, emission, competitive fluorescence studies using EtBr, CD and time-resolved fluorescence studies. Thermodynamic parameters of analogs 5c and 6c with CT-DNA were also calculated at 298, 303 and 308K temperatures by UV–visible spectroscopy. The molecular docking studies give the docking score for all compounds with PDB codes: 1BNA and 2XCT. The MD simulation study of analogs 5c and 6c was also carried out. The pharmacokinetic and ADME properties were calculated for all of the synthesized analogs (5a–5e) and (6a–6h).

Communicated by Ramaswamy H. Sarma

Keywords:

• Schiff base
• pyrazole
• antibacterial
• DNA binding
• MD simulation

Acknowledgments

The authors are thankful to the Centre for Instrumentation Facility (CIF), Jamia Millia Islamia, New Delhi for providing the instruments. RS also thanks to Prof. Moh. Mahfuzul Haque, Department of Biotechnology, JMI for providing UV-visible spectral analysis facility. Also thanks to the University Grant Commission (UGC), New Delhi for Non-NET fellowship.

Authors’ contributions

Razia Sultana: Experimental work, data analysis, investigation, writing original draft. Ashgar Ali: Antibacterial activity, writing original draft. Charmy Twala: MD simulation study. Rabiya Mehandi: Investigation, Data analysis. Manish Rana: Computational studies. Daraksha Yameen: Thermal analysis. Mohammad Abid: Antibacterial activity, writing original draft. Rahisuddin: Methedology, Editing the manuscript, Supervision.

Disclosure statement

The authors declare that they have no known competing financial conflict or personal interests that might have seemed to influenced the work reported in this article.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.