Substituted dihydronaphthalenes as efflux pump inhibitors of Staphylococcus aureus

TY - JOUR

T1 - Substituted dihydronaphthalenes as efflux pump inhibitors of Staphylococcus aureus

AU - Thota, Niranjan

AU - Reddy, Mallepally V

AU - Kumar, Ashwani

AU - Khan, Inshad A

AU - Sangwan, Payare L

AU - Kalia, Nitin P

AU - Koul, Jawahir L

AU - Koul, Surrinder

N1 - 2010 Elsevier Masson SAS. All rights reserved.

PY - 2010/9

Y1 - 2010/9

N2 - A new series of 3-(substituted-3,4-dihydronaphthyl)-2-propenoic acid amides has been prepared through convergent synthetic strategies and tested in combination with ciprofloxacin against NorA overexpressing Staphylococcus aureus 1199B as test strain for potentiating of the drug activity. Out of 24 compounds evaluated, 12 compounds potentiated the activity of ciprofloxacin and resulted in 2-16 fold reduction in the MIC (4-0.5 μg/mL) of the drug. The failure of these efflux pump inhibitors (EPIs) to potentiate the activity of ciprofloxacin when tested against NorA knock out S. aureus SA-K1758 established their identity as NorA inhibitors. The structure of all these newly synthesised compounds was confirmed by spectral data. The present communication describes the synthesis, bioevaluation, structure activity relationship and mechanism of action of these EPIs. Design and synthesis of new series of 3-(substituted 3,4-dihydronaphthyl)- propenoic acid amides as efflux pump inhibitors has resulted in the MIC reduction of ciprofloxacin.

AB - A new series of 3-(substituted-3,4-dihydronaphthyl)-2-propenoic acid amides has been prepared through convergent synthetic strategies and tested in combination with ciprofloxacin against NorA overexpressing Staphylococcus aureus 1199B as test strain for potentiating of the drug activity. Out of 24 compounds evaluated, 12 compounds potentiated the activity of ciprofloxacin and resulted in 2-16 fold reduction in the MIC (4-0.5 μg/mL) of the drug. The failure of these efflux pump inhibitors (EPIs) to potentiate the activity of ciprofloxacin when tested against NorA knock out S. aureus SA-K1758 established their identity as NorA inhibitors. The structure of all these newly synthesised compounds was confirmed by spectral data. The present communication describes the synthesis, bioevaluation, structure activity relationship and mechanism of action of these EPIs. Design and synthesis of new series of 3-(substituted 3,4-dihydronaphthyl)- propenoic acid amides as efflux pump inhibitors has resulted in the MIC reduction of ciprofloxacin.

KW - Anti-Bacterial Agents

KW - Bacterial Proteins

KW - Ciprofloxacin

KW - Drug Synergism

KW - Membrane Transport Proteins

KW - Microbial Sensitivity Tests

KW - Naphthalenes

KW - Staphylococcus aureus

KW - Structure-Activity Relationship

KW - Journal Article

U2 - 10.1016/j.ejmech.2010.05.006

DO - 10.1016/j.ejmech.2010.05.006

M3 - Journal article

C2 - 20605275

SN - 0223-5234

VL - 45

SP - 3607

EP - 3616

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

IS - 9

ER -