DNA binding ligands targeting drug-resistant Gram-positive bacteria. Part 2: C-terminal benzimidazoles and derivatives.
The synthesis and in vitro potency of DNA minor-groove binding antibacterials lacking the C-terminal amide bond are described. The crescent shaped molecules bear the positively charged amino group at an internal pyrrole unit instead of the C-terminus. Three structural parameters were investigated: the N-terminal unit, the internal amino group, and the C-terminal ring system. Several compounds demonstrated good in vitro potency against various Gram-positive bacteria and some molecules were moderately active against Escherichia coli, a representative Gram-negative strain.
Genesoft Pharmaceuticals Inc., 7300 Shoreline Court, South San Francisco, CA 94080, USA.
Roland W
RW
Bürli
Peter
P
Jones
Dustin
D
McMinn
Quan
Q
Le
Jian-Xin
JX
Duan
Jacob A
JA
Kaizerman
Stacey
S
Difuntorum
Heinz E
HE
Moser
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001562:Benzimidazoles / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D024881:Drug Resistance, Bacterial / Q000502:physiology; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000378:metabolism*; D008024:Ligands; D008826:Microbial Sensitivity Tests; D011485:Protein Binding / Q000502:physiology
D000900:Anti-Bacterial Agents; D001562:Benzimidazoles; D008024:Ligands; D004247:DNA