Secondary metabolites by chemical screening. 17. Nigericinol derivatives: synthesis, biological activities, and modeling studies.
The synthesis and the biological activity of C-1-reduced nigericin derivatives (nigericinols) are described and discussed. The dichloronigericinol 7 impressively demonstrated that the C-1 carboxylic acid moiety was not required for a distinct activity against bacteria and viruses. Based on the correlation between K+/H+ antiport activities and antibacterial activities it was deduced that the mode of action of the described nigericinols are related to their ionophoric properties. Molecular modeling studies showed that the efficiency of the nigericinols as ionophores correlates, qualitatively, with the probability of forming a cyclic structure, with the exception of 7.
Grabley
S
S
Hoechst AG, Frankfurt a. Main, Germany.
Hammann
P
P
Klein
R
R
Seibert
G
G
Winkler
I
I
Kröger
A
A
Ditzel
F
F
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008958:Models, Molecular; D015394:Molecular Structure; D009550:Nigericin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018139:Simplexvirus / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D013297:Streptococcus pyogenes / Q000187:drug effects; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000998:Antiviral Agents; C073526:1,30-didehydroxy-1,30-dichloronigericinol; D009550:Nigericin