Antibacterial activity of the marine sponge constituent cribrostatin 6.
The antibacterial activity of the nitrogen heterocyclic sponge constituent cribrostatin 6 was examined. Cribrostatin 6 was bacteriostatic for a variety of Gram-positive species and was bactericidal for the majority of clinical isolates of Streptococcus pneumoniae, including penicillin-resistant strains. Minimum bactericidal concentration/MIC ratios were < or =2 for 75 % of S. pneumoniae clinical isolates. Kill-curve analysis confirmed the bactericidal action of cribrostatin 6. Bactericidal activity was rather slow, beginning at 2, 4 or 8 h, depending on the strain. The frequency of occurrence of bacterial spontaneous mutations to resistance was < or =10(-7). The maximum tolerated dose of cribrostatin 6 in mice was 750-1000 micro g kg(-1) day(-1). Cribrostatin 6 is a promising lead antibiotic for Gram-positive bacteria, particularly S. pneumoniae, a leading cause of infection and mortality worldwide.
Pettit
Robin K
RK
Cancer Research Institute1 and Departments of Microbiology2 and Chemistry and Biochemistry3, Arizona State University, Tempe, AZ 85287-2404, USA 4Microbiology Lab, Phoenix Children's Hospital, Phoenix, AZ 85016, USA.
Fakoury
Bridget R
BR
Cancer Research Institute1 and Departments of Microbiology2 and Chemistry and Biochemistry3, Arizona State University, Tempe, AZ 85287-2404, USA 4Microbiology Lab, Phoenix Children's Hospital, Phoenix, AZ 85016, USA.
Knight
John C
JC
Cancer Research Institute1 and Departments of Microbiology2 and Chemistry and Biochemistry3, Arizona State University, Tempe, AZ 85287-2404, USA 4Microbiology Lab, Phoenix Children's Hospital, Phoenix, AZ 85016, USA.
Weber
Christine A
CA
Cancer Research Institute1 and Departments of Microbiology2 and Chemistry and Biochemistry3, Arizona State University, Tempe, AZ 85287-2404, USA 4Microbiology Lab, Phoenix Children's Hospital, Phoenix, AZ 85016, USA.
Pettit
George R
GR
Cancer Research Institute1 and Departments of Microbiology2 and Chemistry and Biochemistry3, Arizona State University, Tempe, AZ 85287-2404, USA 4Microbiology Lab, Phoenix Children's Hospital, Phoenix, AZ 85016, USA.
Cage
Gary D
GD
Cancer Research Institute1 and Departments of Microbiology2 and Chemistry and Biochemistry3, Arizona State University, Tempe, AZ 85287-2404, USA 4Microbiology Lab, Phoenix Children's Hospital, Phoenix, AZ 85016, USA.
Pon
Sandy
S
Cancer Research Institute1 and Departments of Microbiology2 and Chemistry and Biochemistry3, Arizona State University, Tempe, AZ 85287-2404, USA 4Microbiology Lab, Phoenix Children's Hospital, Phoenix, AZ 85016, USA.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D001681:Biological Assay; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial / Q000235:genetics; D005260:Female; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D008826:Microbial Sensitivity Tests; D009154:Mutation; D011161:Porifera; D011897:Random Allocation; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D003470:Culture Media; D007546:Isoquinolines; C477578:cribrostatin 6