Antibacterial activity of dipeptide constructs of acetylsalicylic acid and nicotinic acid.
Two dipeptide drugs are synthesized utilizing an acetylsalicylic acid or nicotinic acid molecule for the framework. A D-alanine-D-alanine dipeptide moiety is attached to the carbonyl carbon of acetylsalicylic acid (I) and nicotinic acid (II). Dipeptide derivatives (I) and (II) showed significant reduction of Escherichia coli (E. coli) bacterial growth and colony-forming units. A mixture of (I) and (II) induced growth inhibition of 8%, 17.5%, 28%, and 42.5% at concentrations of 100, 200, 300, and 400 microg/mL, respectively. Ampicillin demonstrated much less growth inhibition of this penicillin-resistant E. coli bacteria. Derivatives (I) and (II) showed significant reduction of colony-forming units at concentrations higher than 200 microg/mL, whereas ampicillin showed no significant affect on colony-forming units. Both (I) and (II) produced no violations of the Rule of 5, indicating favorable characteristics for bioavailability. Molecular properties were determined and showed (I) to have a Log Kow of -0.22 with aqueous solubility of 683.8 mg/L, whereas (II) had a Log Kow of -1.00 and aqueous solubility of 6859 mg/L. A mixture of the parent compounds acetyl salicylic acid and nicotinic acid demonstrated some antibacterial activity.
Bartzatt
Ronald
R
Durham Science Center, Laboratory of Pharmaceutical Studies, Department of Chemistry, University of Nebraska, Omaha, Nebraska 68182, USA. bartzatt@mail.unomaha.edu
Cirillo
Suat L G
SL
Cirillo
Jeffrey D
JD
D000667:Ampicillin / Q000737:chemistry / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001241:Aspirin / Q000737:chemistry / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D015169:Colony Count, Microbial; D004151:Dipeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D007202:Indicators and Reagents; D008826:Microbial Sensitivity Tests; D009525:Niacin / Q000737:chemistry / Q000494:pharmacology*; D010403:Penicillin Resistance; D010406:Penicillins / Q000737:chemistry / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D004151:Dipeptides; D007202:Indicators and Reagents; D010406:Penicillins; D009525:Niacin; D000667:Ampicillin; D001241:Aspirin