TY - JOUR
T1 - Simple synthesis of endophenazine G and other phenazines and their evaluation as anti-methicillin-resistant Staphylococcus aureus agents
AU - Conda-Sheridan, Martin
AU - Udumula, Venkatareddy
AU - Endres, Jennifer L.
AU - Harper, Caleb N.
AU - Jaramillo, Lee
AU - Zhong, Haizhen A.
AU - Bayles, Kenneth W.
N1 - Funding Information:
This work was support by the University of Nebraska Medical Center (Start-up funds, MC-S) and by NIH grant number PO1-AI083211 (KB). We thank Dr. David Oupicky for providing resources and space to conduct the cell studies. We thank Janice A. Taylor and James R. Talaska of the Advanced Microscopy Core Facility at the University of Nebraska Medical Center for providing assistance with confocal microscopy. Data reported in this manuscript was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P30 GM106397 . The CARLZEISS LSM is supported by the National Institutes of Health Shared Instrument Grant program: NIH S10-RR-027301 . The NMR Research Facility at UNMC (part of the Fred & Pamela Buffett Cancer Center) is supported by NIH grant number P30-CA036727 .
Publisher Copyright:
© 2016 Elsevier Masson SAS
PY - 2017
Y1 - 2017
N2 - Community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) has become a severe health concern because of its treatment difficulties. Herein, we report the synthesis and biological evaluation of two phenazine natural products and a series of phenazines that show promising activities against MRSA with MIC values in the low micromolar range. Basic studies revealed that these compounds are bacteriostatic agents. The most active compound also displayed promising IC50 values against HaCat cells. Finally, a QSAR model was developed to understand the key structural features of the molecules.
AB - Community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) has become a severe health concern because of its treatment difficulties. Herein, we report the synthesis and biological evaluation of two phenazine natural products and a series of phenazines that show promising activities against MRSA with MIC values in the low micromolar range. Basic studies revealed that these compounds are bacteriostatic agents. The most active compound also displayed promising IC50 values against HaCat cells. Finally, a QSAR model was developed to understand the key structural features of the molecules.
KW - Antibacterial Agents
KW - Bacterial Infections
KW - Drug-resistant Bacteria
KW - MRSA
KW - Methicillin-Resistant Staphylococcus Aureus
KW - Natural Product Synthesis
KW - Phenazines
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U2 - 10.1016/j.ejmech.2016.09.079
DO - 10.1016/j.ejmech.2016.09.079
M3 - Article
C2 - 27721155
AN - SCOPUS:84990818405
SN - 0223-5234
VL - 125
SP - 710
EP - 721
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
ER -