Design, synthesis, in vitro and in silico bioactivity profiles of new urea/thiourea derivatives of 2-pyridyl piperazine as potent antioxidant and antimicrobial agents: chemo-bio-computational approach

Abstract

Synthesis of a series of new urea and thiourea derivatives of 2-pyridyl piperazine was accomplished by reacting various isocyanates and isothiocyanates in the presence of triethylamine (TEA) at 50 °C. All the title compounds were obtained in high yields and their structures were characterized by IR, ¹H, ¹³C NMR, Mass spectral, and Elemental analysis. The synthesized compounds were screened for in vitro and in silico antioxidant and antimicrobial activities. All the title compounds exhibited potent antioxidant and antimicrobial activities. Out of all, 2c and 2f against DPPH, H₂O₂ and Nitro oxide have exhibited significant activity and the levels of activity were higher than the reference compounds, ascorbic acid and BHT. Whereas 2a, 2c, 2f and 2j have shown prominent activity in terms of zone of inhibition against all the microbial strains tested than the standards such as levofloxacin and nystatin. In addition in silico studies also conveyed the same that is 2a, 2c, 2f and 2j have displayed the highest binding energies against peroxiredoxins and DNA gyrase protein than the standards akin to the rest of the compounds. In overall, 2c and 2f have exhibited most promising antioxidant and antimicrobial activity than the rest of the title compounds in vitro and in silico. Hence, 2c and 2f will stand as a lead and promising antioxidant and antimicrobial drug candidates in future.

Communicated by Ramaswamy H. Sarma

Keywords:

• 2-Pyridyl piperazine
• isocyanates
• isothiocyanates
• urea/thiourea derivatives
• antioxidant
• antimicrobial
• in-silico studies

Acknowledgments

The authors are grateful to the Department of Chemistry and Zoology, Sri Venkateswara University, Tirupati for providing lab facilities.

Disclosure statement

The authors declare that there is no conflict of interest.

Funding

The authors confirmed that they have not received any external funding for this work.