Rifamycins inhibit human neutrophil functions: new derivatives with potential antiinflammatory activity.
In our study we investigated the effect of rifamycin SV, rifamycin B, rifampicin and five semisynthetic derivatives on human neutrophil functions such as locomotion, superoxide production and degranulation stimulated by specific agonists. All compounds were tested at concentrations ranging from 10(-9) to 10(-5) M. Among the newly synthesized compounds the most active we found to be the derivatives carrying an acidic substituent at C3: these significantly lowered the superoxide generation induced by PMA throughout the entire concentration range, whereas rifamycin SV, rifamycin B and rifampicin were effective only at the highest concentrations. Moreover, chemotactic movement was significantly attenuated by derivative R4, rifamycin B and rifamycin SV at high doses; granule enzyme release was unaffected by all compounds.
Spisani
S
S
Istituto di Strutturistica Chimica CNR, Roma, Italy.
Traniello
S
S
Martuccio
C
C
Rizzuti
O
O
Cellai
L
L
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015550:Cell Degranulation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006801:Humans; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D016897:Respiratory Burst / Q000187:drug effects; D012294:Rifamycins / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D012294:Rifamycins