[Metalloproteinase inhibition: therapeutic application in rheumatic diseases].
OBJECTIVE
Matrix metalloproteinases (MMPs) play an important role in the degradation of articular cartilage in several diseases, including osteorthritis and rheumatoid arthritis. Aiming at developing new drugs with selective inhibiting action against enzyme damaging the extracellular matrix, research is mainly directed towards the: 1) development of new drugs with specific inhibitory effect on MMPs; 2) better understanding of the pharmacologic profile of drugs already used in the treatment of rheumatic diseases, in order to identify those having an inhibiting action on degradative enzymes.


METHODS
The interaction between rifamycins and collagenase type XI were studied using a fluorogenic substrate MOCAc-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2.


RESULTS
In our experimental conditions rifamycins showed a marked inhibition capacity with a IC50 ranging from 13 to 20.7 microM. This inhibition was reversible after extensive dialysis.


CONCLUSIONS
Our results indicate that the effects of rifamycins in rheumatoid arthritis may correlate to the inhibitory activity of these molecules on collagenase activity.
Barracchini
A
A
Cattedre di Farmacologia, Facoltà di Medicina e Chirurgia, Università degli Studi dell'Aquila, Italia.
Franceschini
N
N
Di Giulio
A
A
Amicosante
G
G
Oratore
A
A
Minisola
G
G
Pantaleoni
G C
GC
D001172:Arthritis, Rheumatoid / Q000628:therapy*; D017364:Collagenases / Q000627:therapeutic use; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D010003:Osteoarthritis / Q000628:therapy*; D012294:Rifamycins / Q000627:therapeutic use; D013938:Thymidine Monophosphate / Q000627:therapeutic use*
D061965:Matrix Metalloproteinase Inhibitors; D012294:Rifamycins; D013938:Thymidine Monophosphate; D017364:Collagenases