64122-23-2Relevant articles and documents
Novel fluorinated pyrrolomycins as potent anti-staphylococcal biofilm agents: Design, synthesis, pharmacokinetics and antibacterial activities
Yang, Zunhua,Liu, Yan,Ahn, Jongsam,Qiao, Zhen,Endres, Jennifer L.,Gautam, Nagsen,Huang, Yunlong,Li, Jerry,Zheng, Jialin,Alnouti, Yazen,Bayles, Kenneth W.,Li, Rongshi
, p. 129 - 137 (2016)
Staphylococcus aureus (SA) is a major cause of hospital- and community-associated bacterial infections in the U.S. and around the world. These infections have become increasingly difficult to treat due to the propensity to develop antibiotic resistance and form biofilm. To date, no antibiofilm agents are available for clinical use. To add to the repertoire of antibiotics for clinical use and to provide novel agents for combating both SA and biofilm infections, we previously reported marinopyrroles as potent anti-SA agents. In this study, we used fragment-based and bioisostere approaches to design and synthesize a series of novel fluorinated pyrrolomycins for the first time, performed analyses of their physicochemical and drug-like properties, and investigated structure activity relationships and pharmacokinetics. These promising fluorinated pyrrolomycins demonstrate potent antibacterial activity against SA with favorable drug-like properties and pharmacokinetic profiles. Importantly, these compounds kill staphylococcal biofilm-associated cells with a lack of mammalian cell cytotoxicity and no occurrence of bacterial resistance. Our novel fluorinated pyrrolomycin 4 has a clogP value of 4.1, an MIC of 73 ng/mL, MBC of 4 μg/mL, kill staphylococcal-associated biofilm at 8 μg/mL, bioavailability of 35%, and the elimination half-life of 6.04 h and 6.75 h by intravenous and oral administration, respectively. This is the first report of comprehensive drug discovery studies on pyrrolomycin-based antibiotics.
PYRROLOMYCINS AND METHODS OF USING THE SAME
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Paragraph 0076, (2017/02/09)
Provided herein are pyrrolomycin derivatives, which can be used to modulate Mcl-1, inhibit proliferation of bacteria and pathogens, as well as to treat infectious diseases and cancers.
Marine Bacteria, I. - Synthesis of Pentabromopseudiline, a Cytotoxic Phenylpyrrole from Alteromonas luteo-violaceus
Laatsch, Hartmut,Pudleiner, Heinz
, p. 863 - 882 (2007/10/02)
A new synthesis of 2,3,4-tribromo-5-(3,5-dibromo-2-hydroxyphenyl)pyrrole (1a, pentabromopseudiline), an antibiotic, enzymeinhibitory and cytotoxic active constituent of the marine bacterium Alteromonas luteo-violaceus, is described.For investigation of structure-activity relationships further 2-phenylpyrroles are investigated.Key step in their synthesis is the Grignard reaction of 2-(1,3-dioxan-2-yl)ethylmagnesium bromide (9d) with benzoyl chlorides yielding γ-phenyl-γ-ketoaldehydes 24, and the Paal-Knorr cyclisation of the latter. - Key Words: Alteromonas luteo-violaceus / Bromopyrrole / Marine bacteria / Pentabromopseudiline
