Abstract
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.
Keywords: Cephalothin, cephalosporins, Escherichia coli, resistant, antibiotic
Medicinal Chemistry
Title: Derivatives of Cephalothin that Inhibit Ampicillin Resistant Escherichia Coli
Volume: 3 Issue: 1
Author(s): Ronald Bartzatt, Suat L G. Cirillo and Jeffrey D. Cirillo
Affiliation:
Keywords: Cephalothin, cephalosporins, Escherichia coli, resistant, antibiotic
Abstract: 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.
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Bartzatt Ronald, G. Cirillo L Suat and Cirillo D. Jeffrey, Derivatives of Cephalothin that Inhibit Ampicillin Resistant Escherichia Coli , Medicinal Chemistry 2007; 3 (1) . https://dx.doi.org/10.2174/157340607779317571
DOI https://dx.doi.org/10.2174/157340607779317571 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
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