Impact of pyridyl moieties on the inhibitory properties of prominent acyclic metal chelators against metallo-β-lactamase-producing Enterobacteriaceae : investigating the molecular basis of acyclic metal chelators' activity
Carbapenem-resistant Enterobacteriaceae (CREs)-mediated infections remain a huge public health concern. CREs produce enzymes such as metallo-β-lactamases (MBLs), which inactivate β-lactam antibiotics. Hence, developing efficient molecules capable of inhibiting these enzymes remains a way forward to...
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sg-ntu-dr.10356-1501782021-06-04T04:18:43Z Impact of pyridyl moieties on the inhibitory properties of prominent acyclic metal chelators against metallo-β-lactamase-producing Enterobacteriaceae : investigating the molecular basis of acyclic metal chelators' activity Sosibo, Sphelele C. Somboro, Anou M. Amoako, Daniel G. Osei Sekyere, John Bester, Linda A. Ngila, Jane C. Sun, Darren Delai Kumalo, Hezekiel M. School of Civil and Environmental Engineering Engineering::Chemical engineering Binding Affinity Enterobacteriaceae Carbapenem-resistant Enterobacteriaceae (CREs)-mediated infections remain a huge public health concern. CREs produce enzymes such as metallo-β-lactamases (MBLs), which inactivate β-lactam antibiotics. Hence, developing efficient molecules capable of inhibiting these enzymes remains a way forward to overcoming this phenomenon. In this study, we demonstrate that pyridyl moieties favor the inhibitory activity of cyclic metal-chelating agents through in vitro screening, molecular modeling, and docking assays. Di-(2-picolyl) amine and tris-(2-picolyl) amine exhibited great efficacy against different types of MBLs and strong binding affinity for NDM-1, whereas 2-picolyl amine did not show activity at a concentration of 64 mg/L in combination with meropenem; it further showed the lowest binding affinity from computational molecular analysis, commensurating with the in vitro screening assays. The findings revealed that the pyridyl group plays a vital role in the inhibitory activity of the tested molecules against CREs and should be exploited as potential MBL inhibitors. 2021-06-04T04:18:42Z 2021-06-04T04:18:42Z 2019 Journal Article Sosibo, S. C., Somboro, A. M., Amoako, D. G., Osei Sekyere, J., Bester, L. A., Ngila, J. C., Sun, D. D. & Kumalo, H. M. (2019). Impact of pyridyl moieties on the inhibitory properties of prominent acyclic metal chelators against metallo-β-lactamase-producing Enterobacteriaceae : investigating the molecular basis of acyclic metal chelators' activity. Microbial Drug Resistance, 25(3), 439-449. https://dx.doi.org/10.1089/mdr.2018.0272 1076-6294 https://hdl.handle.net/10356/150178 10.1089/mdr.2018.0272 30741600 2-s2.0-85064079744 3 25 439 449 en Microbial Drug Resistance © 2019 Mary Ann Liebert, Inc., publishers. All rights reserved. |
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Engineering::Chemical engineering Binding Affinity Enterobacteriaceae Sosibo, Sphelele C. Somboro, Anou M. Amoako, Daniel G. Osei Sekyere, John Bester, Linda A. Ngila, Jane C. Sun, Darren Delai Kumalo, Hezekiel M. Impact of pyridyl moieties on the inhibitory properties of prominent acyclic metal chelators against metallo-β-lactamase-producing Enterobacteriaceae : investigating the molecular basis of acyclic metal chelators' activity |
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Carbapenem-resistant Enterobacteriaceae (CREs)-mediated infections remain a huge public health concern. CREs produce enzymes such as metallo-β-lactamases (MBLs), which inactivate β-lactam antibiotics. Hence, developing efficient molecules capable of inhibiting these enzymes remains a way forward to overcoming this phenomenon. In this study, we demonstrate that pyridyl moieties favor the inhibitory activity of cyclic metal-chelating agents through in vitro screening, molecular modeling, and docking assays. Di-(2-picolyl) amine and tris-(2-picolyl) amine exhibited great efficacy against different types of MBLs and strong binding affinity for NDM-1, whereas 2-picolyl amine did not show activity at a concentration of 64 mg/L in combination with meropenem; it further showed the lowest binding affinity from computational molecular analysis, commensurating with the in vitro screening assays. The findings revealed that the pyridyl group plays a vital role in the inhibitory activity of the tested molecules against CREs and should be exploited as potential MBL inhibitors. |
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School of Civil and Environmental Engineering |
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School of Civil and Environmental Engineering Sosibo, Sphelele C. Somboro, Anou M. Amoako, Daniel G. Osei Sekyere, John Bester, Linda A. Ngila, Jane C. Sun, Darren Delai Kumalo, Hezekiel M. |
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Article |
author |
Sosibo, Sphelele C. Somboro, Anou M. Amoako, Daniel G. Osei Sekyere, John Bester, Linda A. Ngila, Jane C. Sun, Darren Delai Kumalo, Hezekiel M. |
author_sort |
Sosibo, Sphelele C. |
title |
Impact of pyridyl moieties on the inhibitory properties of prominent acyclic metal chelators against metallo-β-lactamase-producing Enterobacteriaceae : investigating the molecular basis of acyclic metal chelators' activity |
title_short |
Impact of pyridyl moieties on the inhibitory properties of prominent acyclic metal chelators against metallo-β-lactamase-producing Enterobacteriaceae : investigating the molecular basis of acyclic metal chelators' activity |
title_full |
Impact of pyridyl moieties on the inhibitory properties of prominent acyclic metal chelators against metallo-β-lactamase-producing Enterobacteriaceae : investigating the molecular basis of acyclic metal chelators' activity |
title_fullStr |
Impact of pyridyl moieties on the inhibitory properties of prominent acyclic metal chelators against metallo-β-lactamase-producing Enterobacteriaceae : investigating the molecular basis of acyclic metal chelators' activity |
title_full_unstemmed |
Impact of pyridyl moieties on the inhibitory properties of prominent acyclic metal chelators against metallo-β-lactamase-producing Enterobacteriaceae : investigating the molecular basis of acyclic metal chelators' activity |
title_sort |
impact of pyridyl moieties on the inhibitory properties of prominent acyclic metal chelators against metallo-β-lactamase-producing enterobacteriaceae : investigating the molecular basis of acyclic metal chelators' activity |
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2021 |
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https://hdl.handle.net/10356/150178 |
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1702431300036591616 |