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MD-045
QSAR,
molecular graphics and modeling study on b-lactam
antibiotics as substrates of the multidrug resistance efflux AcrB pump
Rudolf
Kiralj (PQ), Márcia Miguel Castro Ferreira (PQ)*. marcia@iqm.unicamp.br
Instituto
de Química, Universidade Estadual de Campinas, Campinas 13083-862,
SP, Brasil
Palavras
Chave: multidrug resistance efflux, AcrB bacterial pump, chemometrics
AcrAB-TolC
is the most important multidrug efflux pump of gram-negative bacteria,
which excretes a variety of compounds from bacterial cytoplasm and periplasm
directly to the cell exterior. b-Lactam
antibiotics are also substrates of this pump system, what increases problems
in the treatment of infectious diseases. Chemometric analysis on minimal
inhibitor concentrations (pMIC) elevated by S. typhimurium strains
and of lipophilicity for 16 b-lactams,
as well as QSAR study were performed and completed with docking of selected
drugs to a vestibule and the pore of AcrB transporter component. Two lipophilicity
parameters (logP) in parabolic form, and two electronic and hydrogen bond
descriptors are sufficient to produce parsimonious PLS models. The docking
studies enable visualization of stereoelectronic b-lactam
properties responsible for drug - vestibule and drug - pore recognition
mechanism, thus confirming the QSAR results.
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26a Reunião Anual da Sociedade Brasileira de Química - SBQ