Design, synthesis, and molecular docking study of new piperazine derivative as potential antimicrobial agents

Mahadev Patil; Anurag Noonikara Poyil; Shrinivas D Joshi; Shivaputra A Patil; Siddappa A Patil; Alejandro Bugarin

doi:10.1016/j.bioorg.2019.103217

Design, synthesis, and molecular docking study of new piperazine derivative as potential antimicrobial agents

Bioorg Chem. 2019 Nov:92:103217. doi: 10.1016/j.bioorg.2019.103217. Epub 2019 Aug 26.

Authors

Mahadev Patil¹, Anurag Noonikara Poyil², Shrinivas D Joshi³, Shivaputra A Patil⁴, Siddappa A Patil⁵, Alejandro Bugarin⁶

Affiliations

¹ Centre for Nano & Material Sciences, Jain University, Jain Global Campus, Bangalore 562112, Karnataka, India.
² Department of Chemistry & Biochemistry, University of Texas at Arlington, Arlington, TX 76019, USA.
³ Novel Drug Design and Discovery Laboratory, Department of Pharmaceutical Chemistry, S. E. T's College of Pharmacy, Sangolly Rayanna Nagar, Dharwad 580 002, Karnataka, India.
⁴ Pharmaceutical Sciences Department, College of Pharmacy, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064, USA.
⁵ Centre for Nano & Material Sciences, Jain University, Jain Global Campus, Bangalore 562112, Karnataka, India. Electronic address: p.siddappa@jainuniversity.ac.in.
⁶ Department of Chemistry and Physics, Florida Gulf Coast University, Fort Myers, FL 33965, USA. Electronic address: abugarin@fgcu.edu.

PMID: 31479986
DOI: 10.1016/j.bioorg.2019.103217

Abstract

Herein, we describe the successful design and synthesis of seventeen new 1,4-diazinanes, compounds commonly known as piperazines. This group of piperazine derivatives (3a-q) were fully characterized by ¹H NMR, ¹³C NMR, FT-IR, and LCMS spectral techniques. The molecular structure of piperazine derivative (3h) was further established by single crystal X-ray diffraction analysis. All reported compounds were evaluated for their antibacterial and antifungal potential against five bacterial (Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa) and two fungal strains (Candida albicans and Cryptococcus neoformans). The complete bacterial screening results are provided. As documented, piperazine derivative 3e performed the best against these bacteria. Additionally, data obtained during molecular docking studies are very encouraging with respect to potential utilization of these compounds to help overcome microbe resistance to pharmaceutical drugs, as explicitly noted in this manuscript.

Keywords: Antimicrobial activity; Characterization; Molecular docking; Piperazine derivatives; Synthesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acinetobacter baumannii / drug effects
Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Antifungal Agents / chemical synthesis
Antifungal Agents / chemistry
Antifungal Agents / pharmacology*
Candida albicans / drug effects
Cryptococcus neoformans / drug effects
Dose-Response Relationship, Drug
Drug Design*
Escherichia coli / drug effects
Klebsiella pneumoniae / drug effects
Microbial Sensitivity Tests
Molecular Docking Simulation*
Molecular Structure
Piperazine / chemical synthesis
Piperazine / chemistry
Piperazine / pharmacology*
Pseudomonas aeruginosa / drug effects
Staphylococcus aureus / drug effects
Structure-Activity Relationship

Substances

Anti-Bacterial Agents
Antifungal Agents
Piperazine