Ronald Bartzatt, Suat L G. Cirillo and Jeffrey D. Cirillo Pages 45 - 49 ( 5 )
Two derivatives of cephalothin, compound I and II, were synthesized and demonstrated strong growth inhibition of ampicillin resistant Escherichia coli (E. coli). Compound I is the propyl ester of the parent cephalothin antibiotic, while compound II is the butyl ester derivative. The ester substituent replaces the former carboxyl group of cephalothin. Compounds I and II are stable at room temperature and have increased liphophilicity compared to cephalothin due to the presence of the ester substituent. The MIC50 of I and II were determined to be 55 μg/mL and 30 μg/mL, respectively. Cephalothin showed less than 20% growth inhibition of E. coli at all concentrations based on assay of colony forming units. Compounds I and II showed greater than 50% growth inhibition of E. coli at all concentrations greater than 50 μg/mL (more than 65% at 400 μg/mL). Pharmacological properties such as octanol/water partition Log P and polar surface area were determined. Values for polar surface area suggested 35% of I or II present in the intestinal system would be absorbed. The Log P values for I and II are 2.061 and 2.62, respectively, which indicate I and II will penetrate the blood-brain barrier more effectively than cephalothin. The lipophilic substituent constant (π) for I and II are 1.592 and 1.95, respectively, which indicates the ester substituents contribute a strong lipophilic trait. Properties of molar refractivity, parachor, and molar volume, which describe van-der-Waals interactions, are also determined.
Cephalothin, cephalosporins, Escherichia coli, resistant, antibiotic
University of Nebraska, College of Arts and Sciences, Dept. of Chemistry, 6001 Dodge Street, Omaha, Nebraska 68182, USA.