title: Simple synthesis of endophenazine G and other phenazines and their evaluation as anti-methicillin-resistant Staphylococcus aureus agents.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, United States.
authors.forename: Venkatareddy
authors.initials: V
authors.lastname: Udumula
authors.affiliation: Center for Staphylococcal Research, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, United States.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Endres
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, United States.
authors.forename: Caleb N
authors.initials: CN
authors.lastname: Harper
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, United States.
authors.forename: Lee
authors.initials: L
authors.lastname: Jaramillo
authors.affiliation: Department of Chemistry, University of Nebraska at Omaha, Omaha, NE 68182, United States.
authors.forename: Haizhen A
authors.initials: HA
authors.lastname: Zhong
authors.affiliation: Center for Staphylococcal Research, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, United States.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Bayles
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, United States. Electronic address: martin.condasheridan@unmc.edu.
authors.forename: Martin
authors.initials: M
authors.lastname: Conda-Sheridan
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010619:Phenazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010793:Phthalazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D010619:Phenazines; D010793:Phthalazines; C000616551:endophenzine G
keywords: Antibacterial Agents; Bacterial Infections; Drug-resistant Bacteria; MRSA; Methicillin-Resistant Staphylococcus Aureus; Natural Product Synthesis; Phenazines