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Antibacterial Derivatives of Ciprofloxacin to Inhibit Growth of Necrotizing Fasciitis Associated Penicillin Resistant Escherichia coli.

Bartzatt R, Cirillo SL, Cirillo JD - J Pharm (Cairo) (2013)

Bottom Line: These values of Log P and polar surface area improved tissue penetration, as indicated by the determination of dermal permeability coefficient (K p ) and subsequently into the superficial fascial layer.All drugs induced greater than 60% bacterial cell death at concentrations less than 1.0 micrograms/milliliter.The ester derivatives of ciprofloxacin showed strong antibacterial activity toward penicillin resistant E. coli.

View Article: PubMed Central - PubMed

Affiliation: University of Nebraska, College of Arts & Sciences, Durham Science Center, Department of Chemistry, Omaha, NE 68182, USA.

ABSTRACT
Escherichia coli (E. coli) is associated with necrotizing fasciitis (type I) and can induce enough damage to tissue causing hypoxia. Three ester derivatives of the broad-spectrum antibiotic ciprofloxacin were placed into bacteria culture simultaneously with the parent ciprofloxacin (drug 1) to ascertain the level of antibacterial activity. The n-propyl (drug 2), n-pentyl (drug 3), and n-octyl (drug 4) esters of ciprofloxacin were synthesized under mixed phase conditions and by microwave excitation. The formation of ester derivatives of ciprofloxacin modified important molecular properties such as Log P and polar surface area which improves tissue penetration, yet preserved strong antibacterial activity. The Log P values for drugs 1, 2, 3, and 4 became -0.701, 0.437, 1.50, and 3.02, respectively. The polar surface areas for drugs 1, 2, 3, and 4 were determined to be 74.6 Angstroms(2), 63.6 Angstroms(2), 63.6 Angstroms(2), and 63.6 Angstroms(2), respectively. These values of Log P and polar surface area improved tissue penetration, as indicated by the determination of dermal permeability coefficient (K p ) and subsequently into the superficial fascial layer. All drugs induced greater than 60% bacterial cell death at concentrations less than 1.0 micrograms/milliliter. The ester derivatives of ciprofloxacin showed strong antibacterial activity toward penicillin resistant E. coli.

No MeSH data available.


Related in: MedlinePlus

Enhanced tissue penetration over time period of 7 hours utilizing the dermal permeability coefficient (Kp) and the dermal absorbed dose per event for each compound. Note that the depth of penetration into tissue increases per time period of 7 hours as the length of the ester moiety (aliphatic) increases. The penetration of tissue is greatly enhanced with the placement of an n-octyl ester moiety in place of the original carboxyl group of parent ciprofloxacin. The enhancement of tissue penetration by the n-propyl, n-pentyl, and vast improvement by n-octyl ester derivatives of the broad-spectrum ciprofloxacin will powerfully improve the distribution of the antibacterial medicament within infected tissue.
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fig3: Enhanced tissue penetration over time period of 7 hours utilizing the dermal permeability coefficient (Kp) and the dermal absorbed dose per event for each compound. Note that the depth of penetration into tissue increases per time period of 7 hours as the length of the ester moiety (aliphatic) increases. The penetration of tissue is greatly enhanced with the placement of an n-octyl ester moiety in place of the original carboxyl group of parent ciprofloxacin. The enhancement of tissue penetration by the n-propyl, n-pentyl, and vast improvement by n-octyl ester derivatives of the broad-spectrum ciprofloxacin will powerfully improve the distribution of the antibacterial medicament within infected tissue.

Mentions: Values of Kp for drugs 1 through 4 are shown in Table 3 as rates expressed in centimeter (cm) per hour. Note that the rate of tissue permeation represented at Kp values increases from 2.87E − 05 cm/hour to as high as 26.6E − 03 cm/hour for drug 4 despite the increase of molecular weight of the ciprofloxacin derivatives due to lengthening of the aliphatic ester group (–C(O)OR). As values of Log P increase for each derivative, so does the rate of tissue penetration as represented by Kp. The distance of tissue penetration can be determined over a period of seven hours and plotted for comparison for each ester derivative and parent ciprofloxacin (see Figure 3). Note that all ester derivatives of ciprofloxacin have greater distance of penetration than the parent ciprofloxacin. The enhanced penetration is exceedingly noticed with the n-octyl ester of ciprofloxacin having distance traveled to include 0.0266 cm at one hour and 0.106 cm at four hours. Clearly the ester derivatives enhance penetration by this broad-spectrum antibiotic.


Antibacterial Derivatives of Ciprofloxacin to Inhibit Growth of Necrotizing Fasciitis Associated Penicillin Resistant Escherichia coli.

Bartzatt R, Cirillo SL, Cirillo JD - J Pharm (Cairo) (2013)

Enhanced tissue penetration over time period of 7 hours utilizing the dermal permeability coefficient (Kp) and the dermal absorbed dose per event for each compound. Note that the depth of penetration into tissue increases per time period of 7 hours as the length of the ester moiety (aliphatic) increases. The penetration of tissue is greatly enhanced with the placement of an n-octyl ester moiety in place of the original carboxyl group of parent ciprofloxacin. The enhancement of tissue penetration by the n-propyl, n-pentyl, and vast improvement by n-octyl ester derivatives of the broad-spectrum ciprofloxacin will powerfully improve the distribution of the antibacterial medicament within infected tissue.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4590791&req=5

fig3: Enhanced tissue penetration over time period of 7 hours utilizing the dermal permeability coefficient (Kp) and the dermal absorbed dose per event for each compound. Note that the depth of penetration into tissue increases per time period of 7 hours as the length of the ester moiety (aliphatic) increases. The penetration of tissue is greatly enhanced with the placement of an n-octyl ester moiety in place of the original carboxyl group of parent ciprofloxacin. The enhancement of tissue penetration by the n-propyl, n-pentyl, and vast improvement by n-octyl ester derivatives of the broad-spectrum ciprofloxacin will powerfully improve the distribution of the antibacterial medicament within infected tissue.
Mentions: Values of Kp for drugs 1 through 4 are shown in Table 3 as rates expressed in centimeter (cm) per hour. Note that the rate of tissue permeation represented at Kp values increases from 2.87E − 05 cm/hour to as high as 26.6E − 03 cm/hour for drug 4 despite the increase of molecular weight of the ciprofloxacin derivatives due to lengthening of the aliphatic ester group (–C(O)OR). As values of Log P increase for each derivative, so does the rate of tissue penetration as represented by Kp. The distance of tissue penetration can be determined over a period of seven hours and plotted for comparison for each ester derivative and parent ciprofloxacin (see Figure 3). Note that all ester derivatives of ciprofloxacin have greater distance of penetration than the parent ciprofloxacin. The enhanced penetration is exceedingly noticed with the n-octyl ester of ciprofloxacin having distance traveled to include 0.0266 cm at one hour and 0.106 cm at four hours. Clearly the ester derivatives enhance penetration by this broad-spectrum antibiotic.

Bottom Line: These values of Log P and polar surface area improved tissue penetration, as indicated by the determination of dermal permeability coefficient (K p ) and subsequently into the superficial fascial layer.All drugs induced greater than 60% bacterial cell death at concentrations less than 1.0 micrograms/milliliter.The ester derivatives of ciprofloxacin showed strong antibacterial activity toward penicillin resistant E. coli.

View Article: PubMed Central - PubMed

Affiliation: University of Nebraska, College of Arts & Sciences, Durham Science Center, Department of Chemistry, Omaha, NE 68182, USA.

ABSTRACT
Escherichia coli (E. coli) is associated with necrotizing fasciitis (type I) and can induce enough damage to tissue causing hypoxia. Three ester derivatives of the broad-spectrum antibiotic ciprofloxacin were placed into bacteria culture simultaneously with the parent ciprofloxacin (drug 1) to ascertain the level of antibacterial activity. The n-propyl (drug 2), n-pentyl (drug 3), and n-octyl (drug 4) esters of ciprofloxacin were synthesized under mixed phase conditions and by microwave excitation. The formation of ester derivatives of ciprofloxacin modified important molecular properties such as Log P and polar surface area which improves tissue penetration, yet preserved strong antibacterial activity. The Log P values for drugs 1, 2, 3, and 4 became -0.701, 0.437, 1.50, and 3.02, respectively. The polar surface areas for drugs 1, 2, 3, and 4 were determined to be 74.6 Angstroms(2), 63.6 Angstroms(2), 63.6 Angstroms(2), and 63.6 Angstroms(2), respectively. These values of Log P and polar surface area improved tissue penetration, as indicated by the determination of dermal permeability coefficient (K p ) and subsequently into the superficial fascial layer. All drugs induced greater than 60% bacterial cell death at concentrations less than 1.0 micrograms/milliliter. The ester derivatives of ciprofloxacin showed strong antibacterial activity toward penicillin resistant E. coli.

No MeSH data available.


Related in: MedlinePlus