Synthetic dihydropacidamycin antibiotics: a modified spectrum of activity for the pacidamycin class |
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Authors: | Boojamra Constantine G Lemoine Rémy C Blais Johanne Vernier Nicole G Stein Karin A Magon Angela Chamberland Suzanne Hecker Scott J Lee Ving J |
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Institution: | Essential Therapeutics, Inc. (formerly Microcide Pharmaceuticals, Inc.), 850 Maude Avenue, Mountain View, CA 94043, USA. dboojamra@gilead.com |
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Abstract: | Dihydropacidamycins having an antibacterial spectrum modified from that of the natural product pacidamycins and mureidomycins have been synthesized. Synthetic dihydropacidamycins with noteworthy antibacterial activity against wild-type and resistant Escherichia coli have been identified (MIC=4-8 microg/mL). Some dihydropacidamycins are shown to have activity against multi-resistant clinical strains of Mycobacterium tuberculosis. Compounds of this class are inhibitors of the cell wall biosynthetic enzyme, MraY. |
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