O-prenylated 3-carboxycoumarins as a novel class of 15-LOX-1 inhibitors.

ABSTRACT: Allyloxy, Isopentenyloxy, geranyloxy and farnesyloxy derivatives of 3-carboxycoumarin, at position 5, 6, 7, and 8, were synthesized and their inhibitory potency against human 15-lipoxygenase-1 (human 15-LOX-1) were determined. Among the synthetic coumarins, O-allyl and O-isopentenyl derivatives demonstrated no considerable lipoxygenase inhibition while O-geranyl and O-farnesyl derivatives demonstrated potent inhibitory activity. 5-farnesyloxy-3-carboxycoumarin demonstrated the most potent inhibitory activity by IC50 = 0.74 μM while 6-farnesyloxy-3-carboxycoumarin was the weakest inhibitor among farnesyl analogs (IC50 = 10.4 μM). Bonding affinity of the designed molecular structures toward 15-LOX-1 3D structure complexed with RS75091, as potent 15-LOX-1 inhibitor, was studied by utilizing d

SUBMITTER: Jabbari A 

PROVIDER: S-EPMC5300203 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature