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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

Inhibition of penicillin-resistant Escherichia coli by parent ciprofloxacin and combinations of parent ciprofloxacin with various ester derivatives. Note that the observed bacterial death rate is greater than 60% (e.g., percent survival less than 40%) at concentrations less than 1 microgram per milliliter for all combinations. The rate of bacterial death is greater than 80% at concentrations greater than one microgram per milliliter for all combinations. Ciprofloxacin with ester derivatives incurs bacterial death with the additional benefit of enhanced tissue penetration of the antibacterial. Drug combinations are describe previously (1), (2), (3), (4), and (5).
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fig2: Inhibition of penicillin-resistant Escherichia coli by parent ciprofloxacin and combinations of parent ciprofloxacin with various ester derivatives. Note that the observed bacterial death rate is greater than 60% (e.g., percent survival less than 40%) at concentrations less than 1 microgram per milliliter for all combinations. The rate of bacterial death is greater than 80% at concentrations greater than one microgram per milliliter for all combinations. Ciprofloxacin with ester derivatives incurs bacterial death with the additional benefit of enhanced tissue penetration of the antibacterial. Drug combinations are describe previously (1), (2), (3), (4), and (5).

Mentions: Growth inhibition of penicillin-resistant E. coli was evaluated via in vitro addition of known amounts of ciprofloxacin with/without derivatives in the presence of E. coli. The ester derivatives were combined with parent ciprofloxacin individually then as a mixture to demonstrate the efficacy of administering broad-spectrum antimicrobials having multiple levels of Log P (i.e., multiple levels of cell membrane penetration). The outcome of in vitro titration of drugs 1 through 4 showed extremely strong bacterial inhibition even to concentration level below one microgram per milliliter (see Figure 2). The results show that all combinations of drugs (ciprofloxacin plus drug 2 or drug 3 or drug 4) and the mixture of all four drugs (ciprofloxacin and drug 2, 3, 4) induced greater than 80% bacterial death at one microgram per milliliter concentration. The five iterations of drug + bacteria were as follows: (1) ciprofloxacin alone (more than 80% bacteria death at one microgram/milliliter); (2) ciprofloxacin plus drug 2 (more than 80% bacteria death at one microgram/milliliter); (3) ciprofloxacin plus drug 3 (more than 80% bacteria death at one microgram/milliliter); (4) ciprofloxacin plus drug 4 (more than 80% bacteria death at one microgram/milliliter); and (5) all drugs combined (more than 80% bacteria death at one microgram/milliliter). The extent of bacterial death remains greater than 80% across the concentration range of one microgram per milliliter to eight micrograms per milliliter. Figure 2 shows clearly a profound bacterial inhibition at very low concentrations for these drug combinations and a demonstration of the efficacy of multiple levels of Log P (e.g., cell membrane penetration) internal to this broad-spectrum antibiotic. In addition to Figure 2 the numerical values of reduced bacterial survival is presented in Table 2 as percent of survival to concentration for each of ciprofloxacin and it's combination with ester derivatives. These numerical values for decreased bacterial survival (plotted in Figure 2) indicate clearly that the combination of ciprofloxacin with various ester derivatives expresses very strong bacterial growth inhibition. In addition, the enhanced tissue penetration by derivatives of ciprofloxacin is then anticipated to improve antibacterial activity.


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)

Inhibition of penicillin-resistant Escherichia coli by parent ciprofloxacin and combinations of parent ciprofloxacin with various ester derivatives. Note that the observed bacterial death rate is greater than 60% (e.g., percent survival less than 40%) at concentrations less than 1 microgram per milliliter for all combinations. The rate of bacterial death is greater than 80% at concentrations greater than one microgram per milliliter for all combinations. Ciprofloxacin with ester derivatives incurs bacterial death with the additional benefit of enhanced tissue penetration of the antibacterial. Drug combinations are describe previously (1), (2), (3), (4), and (5).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Inhibition of penicillin-resistant Escherichia coli by parent ciprofloxacin and combinations of parent ciprofloxacin with various ester derivatives. Note that the observed bacterial death rate is greater than 60% (e.g., percent survival less than 40%) at concentrations less than 1 microgram per milliliter for all combinations. The rate of bacterial death is greater than 80% at concentrations greater than one microgram per milliliter for all combinations. Ciprofloxacin with ester derivatives incurs bacterial death with the additional benefit of enhanced tissue penetration of the antibacterial. Drug combinations are describe previously (1), (2), (3), (4), and (5).
Mentions: Growth inhibition of penicillin-resistant E. coli was evaluated via in vitro addition of known amounts of ciprofloxacin with/without derivatives in the presence of E. coli. The ester derivatives were combined with parent ciprofloxacin individually then as a mixture to demonstrate the efficacy of administering broad-spectrum antimicrobials having multiple levels of Log P (i.e., multiple levels of cell membrane penetration). The outcome of in vitro titration of drugs 1 through 4 showed extremely strong bacterial inhibition even to concentration level below one microgram per milliliter (see Figure 2). The results show that all combinations of drugs (ciprofloxacin plus drug 2 or drug 3 or drug 4) and the mixture of all four drugs (ciprofloxacin and drug 2, 3, 4) induced greater than 80% bacterial death at one microgram per milliliter concentration. The five iterations of drug + bacteria were as follows: (1) ciprofloxacin alone (more than 80% bacteria death at one microgram/milliliter); (2) ciprofloxacin plus drug 2 (more than 80% bacteria death at one microgram/milliliter); (3) ciprofloxacin plus drug 3 (more than 80% bacteria death at one microgram/milliliter); (4) ciprofloxacin plus drug 4 (more than 80% bacteria death at one microgram/milliliter); and (5) all drugs combined (more than 80% bacteria death at one microgram/milliliter). The extent of bacterial death remains greater than 80% across the concentration range of one microgram per milliliter to eight micrograms per milliliter. Figure 2 shows clearly a profound bacterial inhibition at very low concentrations for these drug combinations and a demonstration of the efficacy of multiple levels of Log P (e.g., cell membrane penetration) internal to this broad-spectrum antibiotic. In addition to Figure 2 the numerical values of reduced bacterial survival is presented in Table 2 as percent of survival to concentration for each of ciprofloxacin and it's combination with ester derivatives. These numerical values for decreased bacterial survival (plotted in Figure 2) indicate clearly that the combination of ciprofloxacin with various ester derivatives expresses very strong bacterial growth inhibition. In addition, the enhanced tissue penetration by derivatives of ciprofloxacin is then anticipated to improve antibacterial activity.

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