Document Detail


Design of ciprofloxacin derivatives that inhibit growth of methicillin resistant Staphylococcus aureus (MRSA) and methicillin susceptible Staphylococcus aureus (MSSA).
MedLine Citation:
PMID:  20367615     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Three derivatives of ciprofloxacin (compound B, C, and D) were constructed utilizing microwave synthesis methodology (compound D) or diazoalkane reaction in nonaqueous solvent (compounds B and C). The final structures of the derivatives featured an ester group in place of the original carboxyl group of the ciprofloxacin. These ester groups contained aliphatic single carbon (compound B), two carbon length (compound C), or three carbon length propyl ester group (compound D). The ester groups strongly affected the molecular properties of the parent ciprofloxacin. As the size of the ester group increased the formula weight, molar volume, and number of rotatable bonds increased. The Log P for these compounds were -0.701, -0.441, -0.065, 0.437 for ciprofloxacin, B, C, and compound D, respectively. Numerical values of dermal permeability coefficient (Kp) increased rapidly as length of the ester carbon chain increased. The immediate consequence of Kp increase is an increased skin penetration rate based on dose and time span of administration. Polar surface area for ciprofloxacin is 74.569 Angstroms(2), but decreases to 63.575 Angstroms(2) for all three derivatives. All three derivatives of ciprofloxacin showed zero violations of the Rule of 5, indicating these drugs would have favorable bioavailability. Compounds A, B, C, and D were placed into tissue culture with methicillin resistant and susceptible Staphylococcus aureus (MRSA and MSSA, respectively) to determine levels of bacterial growth inhibition. All compounds induced greater than 60 % inhibition of MSSA at concentrations as low as 15.63 micrograms/milliliter. All four compounds induced greater than 80 % inhibition of MRSA at concentratins as low as 15.63 micrograms/milliliter. Development of novel drug designs will benefit the clinical treatment of dangerous infections of MSSA and MRSA.
Authors:
Ronald Bartzatt; Suat L G Cirillo; Jeffrey D Cirillo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Medicinal chemistry (Shāriqah (United Arab Emirates))     Volume:  6     ISSN:  1875-6638     ISO Abbreviation:  Med Chem     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-05-17     Completed Date:  2010-09-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101240303     Medline TA:  Med Chem     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  51-6     Citation Subset:  IM    
Affiliation:
University of Nebraska, College of Arts & Sciences, Durham Science Center, Chemistry Department, 6001 Dodge Street, Omaha, Nebraska 68182, USA. rbartzatt@mail.unomaha.edu
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MeSH Terms
Descriptor/Qualifier:
Ciprofloxacin / chemical synthesis,  chemistry,  pharmacology*
Drug Design*
Methicillin / pharmacology*
Methicillin-Resistant Staphylococcus aureus / drug effects*,  growth & development*
Microbial Sensitivity Tests
Models, Molecular
Molecular Structure
Staphylococcus aureus / drug effects*,  growth & development*
Stereoisomerism
Structure-Activity Relationship
Chemical
Reg. No./Substance:
61-32-5/Methicillin; 85721-33-1/Ciprofloxacin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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