Molecular properties and antibacterial activity of the methyl and ethyl ester derivatives of ampicillin.
Ampicillin is a beta-lactam antibiotic that is effective against gram-negative bacteria. Ampicillin has a single carboxyl group (-C(O)OH) within its structure which is suitable for forming ester compounds. Diazomethane and diazoethane were utilized to react with ampicillin to form the methyl and ethyl esters, respectively. The ester derivatives of ampicillin were solubilized together (mole ratio 1:1) in LB media and penicillin resistant Escherichia coli added to measure antibacterial activity. Growth inhibition of bacteria was monitored by optical density after a known time period and with known specific concentrations of the ampicillin esters present. Significant growth inhibition of penicillin resistant bacteria occurred at concentrations of the combined methyl and ethyl ampicillin esters from less than 50 microgram/mL to more than 150 microgram/mL. Molecular properties of the ester compounds were determined. The two ester derivatives showed values of Log BB, Log P, polar surface area, intestinal absorption, and solubility suitable for clinical application. The two ester compounds showed zero violations of the Rule of 5 indicating good bioavailability. The two ester derivatives showed greater intestinal absorbance and greater penetration of the blood brain barrier than the parent ampicillin. Favorable druglikeness was determined for both ester derivatives.
Bartzatt
Ronald
R
University of Nebraska, College of Arts and Sciences, Medicinal Chemistry Laboratory, Omaha, Nebraska 68182, USA. bartzatt@mail.unomaha.edu
Cirillo
Suat L G
SL
Cirillo
Jeffrey D
JD
D000667:Ampicillin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D004926:Escherichia coli / Q000166:cytology / Q000187:drug effects*; D015394:Molecular Structure; D010403:Penicillin Resistance
D000900:Anti-Bacterial Agents; D000667:Ampicillin