Synthetic dihydropacidamycin antibiotics: a modified spectrum of activity for the pacidamycin class.
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.
Boojamra
Constantine G
CG
Essential Therapeutics, Inc. (formerly Microcide Pharmaceuticals, Inc.), 850 Maude Avenue, Mountain View, CA 94043, USA. dboojamra@gilead.com
Lemoine
Rémy C
RC
Blais
Johanne
J
Vernier
Nicole G
NG
Stein
Karin A
KA
Magon
Angela
A
Chamberland
Suzanne
S
Hecker
Scott J
SJ
Lee
Ving J
VJ
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D006088:Gram-Negative Aerobic Bacteria / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D010455:Peptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D010455:Peptides; D011741:Pyrimidine Nucleosides; C432124:dihydropacidamycin D