Abstract
Metalloproteases are a family of zinc-containing endopeptidases involved in a variety
of pathological disorders. The use of flavonoid derivatives as potential metalloprotease
inhibitors has recently increased.
Particular plants growing in Sicily are an excellent yielder of the flavonoids luteolin,
apigenin, and their respective glycoside derivatives (7-O-rutinoside, 7-O-glucoside,
and 7-O-glucuronide).
The inhibitory activity of luteolin, apigenin, and their respective glycoside derivatives
on the metalloproteases MMP-1, MMP-3, MMP-13, MMP-8, and MMP-9 was assessed and rationalized
correlating in vitro target-oriented screening and in silico docking.
The flavones apigenin, luteolin, and their respective glucosides have good ability
to interact with metalloproteases and can also be lead compounds for further development.
Glycones are more active on MMP-1, -3, -8, and -13 than MMP-9. Collagenases MMP-1,
MMP-8, and MMP-13 are inhibited by compounds having rutinoside glycones. Apigenin
and luteolin are inactive on MMP-1, -3, and -8, which can be interpreted as a better
selectivity for both -9 and -13 peptidases. The more active compounds are apigenin-7-O-rutinoside
on MMP-1 and luteolin-7-O-rutinoside on MMP-3. The lowest IC50 values were also found for apigenin-7-O-glucuronide, apigenin-7-O-rutinoside, and
luteolin-7-O-glucuronide. The glycoside moiety might allow for a better anchoring
to the active site of MMP-1, -3, -8, -9, and -13. Overall, the in silico data are substantially in agreement with the in vitro ones (fluorimetric assay).
Key words
Cynara cardunculus var.
scolymus L. - Asteraceae - plant extracts - metalloprotease - flavonoids - glycosides
