Fluoroquinolone-3-carboxamide Amino Acid Conjugates: Synthesis, Antibacterial Properties And Molecular Modeling Studies

Riham M Bokhtia; Siva S Panda; Adel S Girgis; Hitesh H Honkanadavar; Tarek S Ibrahim; Riham F George; Mona T Kashef; Walid Fayad; Rajeev Sakhuja; Eatedal H Abdel-Aal; Amany M M Al-Mahmoudy

doi:10.2174/1573406415666190904143852

Fluoroquinolone-3-carboxamide Amino Acid Conjugates: Synthesis, Antibacterial Properties And Molecular Modeling Studies

Med Chem. 2021;17(1):71-84. doi: 10.2174/1573406415666190904143852.

Affiliations

¹ Department of Chemistry & Physics, Augusta University, Augusta, GA 30912, United States.
² Department of Pesticide Chemistry, National Research Centre, Dokki, Giza 12622, Egypt.
³ Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.
⁴ Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
⁵ Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
⁶ Drug Bioassay-Cell Culture Laboratory, Pharmacognosy Department, National Research Centre, Dokki, Giza, 12622, Egypt.
⁷ Department of Chemistry, Birla Institute of Technology and Science, Pilani 333 031, Rajasthan, India.

PMID: 31483233
DOI: 10.2174/1573406415666190904143852

Abstract

Background: Bacterial infections are considered as one of the major global health threats, so it is very essential to design and develop new antibacterial agents to overcome the drawbacks of existing antibacterial agents.

Methods: The aim of this work is to synthesize a series of new fluoroquinolone-3-carboxamide amino acid conjugates by molecular hybridization. We utilized benzotriazole chemistry to synthesize the desired hybrid conjugates.

Results: All the conjugates were synthesized in good yields, characterized, evaluated for their antibacterial activity. The compounds were screened for their antibacterial activity using methods adapted from the Clinical and Laboratory Standards Institute. Synthesized conjugates were tested for activity against medically relevant pathogens; Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27856) Staphylococcus aureus (ATCC 25923) and Enterococcus faecalis (ATCC 19433).

Conclusion: The observed antibacterial experimental data indicates the selectivity of our synthesized conjugates against E.Coli. The protecting group on amino acids decreases the antibacterial activity. The synthesized conjugates are non-toxic to the normal cell lines. The experimental data were supported by computational studies.

Keywords: Antibacterial agents; amino acid; antimicrobial; conjugates; fluoroquinolone; molecular modeling.

MeSH terms

Amino Acids / chemistry*
Anti-Bacterial Agents / chemical synthesis*
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Cell Line
Chemistry Techniques, Synthetic
Fluoroquinolones / chemical synthesis*
Fluoroquinolones / chemistry
Fluoroquinolones / pharmacology*
Microbial Sensitivity Tests
Models, Molecular*
Molecular Conformation
Structure-Activity Relationship

Substances

Amino Acids
Anti-Bacterial Agents
Fluoroquinolones