Synthesis and molecular modeling of antimicrobial active fluoroquinolone-pyrazine conjugates with amino acid linkers

Siva S Panda; Oleksandr S Detistov; Adel S Girgis; Prabhu P Mohapatra; Ahmed Samir; Alan R Katritzky

doi:10.1016/j.bmcl.2016.03.062

Synthesis and molecular modeling of antimicrobial active fluoroquinolone-pyrazine conjugates with amino acid linkers

Bioorg Med Chem Lett. 2016 May 1;26(9):2198-205. doi: 10.1016/j.bmcl.2016.03.062. Epub 2016 Mar 16.

Authors

Siva S Panda¹, Oleksandr S Detistov², Adel S Girgis³, Prabhu P Mohapatra⁴, Ahmed Samir⁵, Alan R Katritzky²

Affiliations

¹ Department of Chemistry & Physics, Augusta University, Augusta, GA 30912, USA. Electronic address: sspanda12@gmail.com.
² Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA.
³ Pesticide Chemistry Department, National Research Centre, Dokki, Giza 12622, Egypt.
⁴ Department of Chemistry & Physics, Augusta University, Augusta, GA 30912, USA.
⁵ Microbiology Department, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt.

PMID: 27025339
DOI: 10.1016/j.bmcl.2016.03.062

Abstract

Novel fluoroquinolone-pyrazine conjugates 7a-h with amino acid linkers were synthesized in good yields utilizing benzotriazole chemistry. Antimicrobial bioassay showed that the synthesized bis-conjugates have antimicrobial properties comparable to the parent drugs. Compound 7h showed superior antibacterial activity against Staphylococcus aureus and Streptococcus pyogenes (MIC=74.6 μM and 149.3 μM, respectively). This matched well with the estimated values obtained from 3D-pharmacophore and 2D-QSAR studies (MIC=67 μM and 92.9 μM, respectively).

Keywords: Antibiotics; Benzotriazole chemistry; Computational studies; Conjugates.

Publication types

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

MeSH terms

Amino Acids / chemical synthesis
Amino Acids / chemistry
Amino Acids / pharmacology
Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / chemistry*
Anti-Bacterial Agents / pharmacology
Fluoroquinolones / chemical synthesis*
Fluoroquinolones / chemistry
Fluoroquinolones / pharmacology
Models, Molecular
Piperazines / chemical synthesis
Piperazines / chemistry*
Piperazines / pharmacology
Pseudomonas aeruginosa / drug effects
Pyrazines / chemical synthesis
Pyrazines / chemistry*
Pyrazines / pharmacology
Quantitative Structure-Activity Relationship
Quinolines / chemical synthesis
Quinolines / chemistry*
Quinolines / pharmacology
Salmonella typhi / drug effects
Staphylococcus aureus / drug effects
Streptococcus pyogenes / drug effects
Triazoles / chemistry

Substances

1-cyclopropyl-6-fluoro-4-oxo-7-(4-(4-(pyrazine-2-carboxamido)butanoyl)piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid
Amino Acids
Anti-Bacterial Agents
Fluoroquinolones
Piperazines
Pyrazines
Quinolines
Triazoles