Tags

Type your tag names separated by a space and hit enter

Binding site feature description of 2-substituted benzothiazoles as potential AcrAB-TolC efflux pump inhibitors in E. coli.
SAR QSAR Environ Res 2015; 26(10):853-71SQ

Abstract

The resistance-nodulation-division (RND) family efflux pumps are important in the antibiotic resistance of Gram-negative bacteria. However, although a number of bacterial RND efflux pump inhibitors have been developed, there has been no clinically available RND efflux pump inhibitor to date. A set of BSN-coded 2-substituted benzothiazoles were tested alone and in combinations with ciprofloxacin (CIP) against the AcrAB-TolC overexpressor Escherichia coli AG102 clinical strain. The results indicated that the BSN compounds did not show intrinsic antimicrobial activity when tested alone. However, when used in combinations with CIP, a reversal in the antibacterial activity of CIP with up to 10-fold better MIC values was observed. In order to describe the binding site features of these BSN compounds with AcrB, docking studies were performed using the CDocker method. The performed docking poses and the calculated binding energy scores revealed that the tested compounds BSN-006, BSN-023, and BSN-004 showed significant binding interactions with the phenylalanine-rich region in the distal binding site of the AcrB binding monomer. Moreover, the tested compounds BSN-006 and BSN-023 possessed stronger binding energies than CIP, verifying that BSN compounds are acting as the putative substrates of AcrB.

Authors+Show Affiliations

a Pharmaceutical Chemistry Department, Faculty of Pharmacy , Ankara University , Ankara , Turkey.b Medical Microbiology Department, Faculty of Medicine , Marmara University , Istanbul , Turkey.a Pharmaceutical Chemistry Department, Faculty of Pharmacy , Ankara University , Ankara , Turkey.b Medical Microbiology Department, Faculty of Medicine , Marmara University , Istanbul , Turkey.b Medical Microbiology Department, Faculty of Medicine , Marmara University , Istanbul , Turkey.a Pharmaceutical Chemistry Department, Faculty of Pharmacy , Ankara University , Ankara , Turkey.a Pharmaceutical Chemistry Department, Faculty of Pharmacy , Ankara University , Ankara , Turkey.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26559566

Citation

Yilmaz, S, et al. "Binding Site Feature Description of 2-substituted Benzothiazoles as Potential AcrAB-TolC Efflux Pump Inhibitors in E. Coli." SAR and QSAR in Environmental Research, vol. 26, no. 10, 2015, pp. 853-71.
Yilmaz S, Altinkanat-Gelmez G, Bolelli K, et al. Binding site feature description of 2-substituted benzothiazoles as potential AcrAB-TolC efflux pump inhibitors in E. coli. SAR QSAR Environ Res. 2015;26(10):853-71.
Yilmaz, S., Altinkanat-Gelmez, G., Bolelli, K., Guneser-Merdan, D., Ufuk Over-Hasdemir, M., Aki-Yalcin, E., & Yalcin, I. (2015). Binding site feature description of 2-substituted benzothiazoles as potential AcrAB-TolC efflux pump inhibitors in E. coli. SAR and QSAR in Environmental Research, 26(10), pp. 853-71. doi:10.1080/1062936X.2015.1106581.
Yilmaz S, et al. Binding Site Feature Description of 2-substituted Benzothiazoles as Potential AcrAB-TolC Efflux Pump Inhibitors in E. Coli. SAR QSAR Environ Res. 2015;26(10):853-71. PubMed PMID: 26559566.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Binding site feature description of 2-substituted benzothiazoles as potential AcrAB-TolC efflux pump inhibitors in E. coli. AU - Yilmaz,S, AU - Altinkanat-Gelmez,G, AU - Bolelli,K, AU - Guneser-Merdan,D, AU - Ufuk Over-Hasdemir,M, AU - Aki-Yalcin,E, AU - Yalcin,I, PY - 2015/11/13/entrez PY - 2015/11/13/pubmed PY - 2016/8/17/medline KW - AcrAB-TolC KW - AcrB docking KW - E. coli AG102 KW - EPI KW - benzothiazoles KW - ciprofloxacin SP - 853 EP - 71 JF - SAR and QSAR in environmental research JO - SAR QSAR Environ Res VL - 26 IS - 10 N2 - The resistance-nodulation-division (RND) family efflux pumps are important in the antibiotic resistance of Gram-negative bacteria. However, although a number of bacterial RND efflux pump inhibitors have been developed, there has been no clinically available RND efflux pump inhibitor to date. A set of BSN-coded 2-substituted benzothiazoles were tested alone and in combinations with ciprofloxacin (CIP) against the AcrAB-TolC overexpressor Escherichia coli AG102 clinical strain. The results indicated that the BSN compounds did not show intrinsic antimicrobial activity when tested alone. However, when used in combinations with CIP, a reversal in the antibacterial activity of CIP with up to 10-fold better MIC values was observed. In order to describe the binding site features of these BSN compounds with AcrB, docking studies were performed using the CDocker method. The performed docking poses and the calculated binding energy scores revealed that the tested compounds BSN-006, BSN-023, and BSN-004 showed significant binding interactions with the phenylalanine-rich region in the distal binding site of the AcrB binding monomer. Moreover, the tested compounds BSN-006 and BSN-023 possessed stronger binding energies than CIP, verifying that BSN compounds are acting as the putative substrates of AcrB. SN - 1029-046X UR - https://www.unboundmedicine.com/medline/citation/26559566/Binding_site_feature_description_of_2_substituted_benzothiazoles_as_potential_AcrAB_TolC_efflux_pump_inhibitors_in_E__coli_ L2 - http://www.tandfonline.com/doi/full/10.1080/1062936X.2015.1106581 DB - PRIME DP - Unbound Medicine ER -