Synthesis and antibacterial evaluation of amino acid-antibiotic conjugates

Mohamed A Ibrahim; Siva S Panda; Antoinette S Birs; Juan C Serrano; Claudio F Gonzalez; Khalid A Alamry; Alan R Katritzky

doi:10.1016/j.bmcl.2014.01.065

Synthesis and antibacterial evaluation of amino acid-antibiotic conjugates

Bioorg Med Chem Lett. 2014 Apr 1;24(7):1856-61. doi: 10.1016/j.bmcl.2014.01.065. Epub 2014 Jan 30.

Authors

Mohamed A Ibrahim¹, Siva S Panda², Antoinette S Birs³, Juan C Serrano², Claudio F Gonzalez³, Khalid A Alamry⁴, Alan R Katritzky⁵

Affiliations

¹ Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, United States; Department of Organic Chemistry, College of Pharmacy, Misr University for Science and Technology, Al-Motamayez District, PO Box 77, Egypt.
² Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, United States.
³ Department of Microbiology and Cell Science, University of Florida, Gainesville, FL 32611-7200, United States.
⁴ Chemistry Department, King Abdulaziz University, Jeddah 21589 Saudi Arabia.
⁵ Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, United States; Chemistry Department, King Abdulaziz University, Jeddah 21589 Saudi Arabia. Electronic address: [email protected].

PMID: 24641976
DOI: 10.1016/j.bmcl.2014.01.065

Abstract

Amino acid conjugates of quinolone, metronidazole and sulfadiazine antibiotics were synthesized in good yields using benzotriazole methodology. All the conjugates were screened for their antibacterial activity using methods adapted from the Clinical and Laboratory Standards Institute. Antibiotic conjugates were tested for activity in four medically relevant organisms; Staphylococcus aureus (RN4220), Escherichia coli (DH5α), Pseudomonas aeruginosa (PAO1), and Bacillus subtilis (168). Several antibiotic conjugates show promising results against several of the strains screened.

Keywords: Antibacterial; Antibiotics; Benzotriazole; Conjugates; Lipophilicity.

Publication types

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

MeSH terms

Amino Acids / chemistry*
Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Bacillus subtilis / drug effects
Dose-Response Relationship, Drug
Escherichia coli / drug effects
Metronidazole / chemical synthesis
Metronidazole / chemistry
Metronidazole / pharmacology*
Microbial Sensitivity Tests
Molecular Structure
Pseudomonas aeruginosa / drug effects
Quinolones / chemical synthesis
Quinolones / chemistry
Quinolones / pharmacology*
Staphylococcus aureus / drug effects
Structure-Activity Relationship
Sulfadiazine / chemical synthesis
Sulfadiazine / chemistry
Sulfadiazine / pharmacology*

Substances

Amino Acids
Anti-Bacterial Agents
Quinolones
Sulfadiazine
Metronidazole