Division of Medicinal Chemistry Abstracts-235th ACS National ...

We synthesized E41, an antibiotic conjugated to a bisphosphonate, which binds CP, creating
targeted drug delivery. E41 bound to bone-homeostatic CP and packed into traumatized bone,
may prevent OM. We contrasted two CPs, µ-sized Skelite and nm-sized NanOss. Adult rats
received traumatic open tibial fracture with medullary contamination by Staphylococcus aureus
(Sa), lavage, E41-CPs packed into the defect, and sacrificed at day 1. Tibial loads, expressed
as log10 colony-forming units/gm, were: Infection controls, 4.40±0.9, E41-Skelite, 2.70±2.0, and
E41-NanOss, 1.10±1.3 (p≤0.01). E41-NanOss produced significantly lower tibial loads vs. E41-
Skelite (p=0.001). Sixteen of 16 Infection-control tibiae yielded bacteria, with high tibial loads,
suggesting developing acute OM; E41-NanOss group, 16 of 19 tibiae sterile vs. 5 of 18 for E41-
Skelite (p=0.0005). NanOss appears to be a better carrier for E41, than Skelite, perhaps
due to its higher particle surface area. E41-NanOss eradicated Sa infection in traumatized bone.
MEDI 29
First small molecule inhibitors of RecA in living bacteria
Anna V. Gromova, Tim J. Wigle, and Scott F. Singleton, School of Pharmacy, Division of
Medicinal Chemistry and Natural Products, University of North Carolina, CB #7360, Chapel Hill,
NC 27599, gromova@email.unc.edu
Antibiotic resistance in bacteria is an escalating threat. RecA facilitates the development and
transmission of antibiotic resistance genes, and promotes survival of bactericidal chemotherapy.
We identified, synthesized, and tested several members of different classes of small molecules
towards inhibition of the RecA protein. Initial leads came from high-throughput screening in
collaboration with the BRITE Institute of North Carolina Central University. We report the first
small molecules capable of inhibiting the bacterial SOS response in live bacteria resulting from
exposure to Ciprofloxacin and appear to do so by inhibiting the RecA protein (IC50 < 10 µM).
MEDI 30
Methods for purifying and detoxifying sodium dodecyl sulfate-stabilized polyacrylate
nanoparticles
Julio Cesar Garay 1 , Danielle Gergeres 1 , Ashley Young 2 , and Edward Turos 1 . (1) Department of
Chemistry, University of South Florida, 4202 E.Fowler Ave., NES 330, Tampa, FL 33620,
jgarayji@mail.usf.edu, (2) Department of Chemistry, student, Tampa, FL 33620
The tremendous impact that antibiotics have had on human health is well-appreciated.
However, many microorganisms have rapidly acquired resistance for most of the currently
available antimicrobials, displaying an amazing versatility to overcome the cidal or static effects
of antibiotics on microbial growth and proliferation. The continuing rise in the numbers and
prevalence of drug-resistant microbes that cause infections, most notably methicillin-resistant
Staphylococcus aureus (MRSA), is further exasperated by the sheer difficulty and expense of
developing new antimicrobially-active molecules. Moreover, many of the most promising drug
candidates suffer from poor water solubility and systemic stability that limits their clinical
development. Our laboratory has been working on ways to improve the performance of such
antibiotic compounds, and for enhancing the activity of older classes of antibiotics, using
polyacrylate nanoparticles. These nanoparticles can be easily prepared by emulsion