Isoflavans Derivatives as Inhibitors of Soybean Lipoxygenase: In-Vitro and Docking Studies

Abstract

The lipoxygenases (LOX) are a family of non-heme iron-containing dioxygenases which catalyze the stereospecific insertion of molecular oxygen into arachidonic acid, leading to hydroxy derivatives as end products. In this work, we studied the behavior of seven isoflavans on 15-soybean lipoxygenases (15-sLOX), comparing them with the known inhibitors quercetin and 3, 4-dihydroxybenzoic acid. Four of the seven investigated isoflavans showed IC 50 values smaller than 50 µM, being more potent than quercetin or 3, 4-dihydroxybenzoic acid. Besides a catecholic pattern, the presence of an aromatic ring B seems to confer additional activity to these compounds, a result which was rationalized by docking studies of these isoflavanss into the enzyme binding site.

Enzymatic Studies of Isoflavonoids as Selective and Potent Inhibitors of Human Leukocyte 5‐Lipo‐Oxygenase

“…The role of the catechol moiety in the LOX inhibitors was previously investigated , but the impact of its position for IR (isoflavones) and HIR (isoflavans) derivatives on the biological activity against human 5‐LOX has not been fully discussed. Of the current 26 derivatives, only the compounds that possessed a catechol moiety manifested submicromolar potency, indicative of either a chelative or reductive inhibitory mechanism.…”

Coumarins of Haplopappus Multifolius and Derivative as Inhibitors of Lox: Evaluation in-Vitro and Docking Studies

“…2 has well interaction of alcoholic geranyl group with non-heme iron (Fe 3+ ) Besides a two hydrogen bridges interaction with amino acid residues, due to a flat structure of the aromatic system, causing inhibition of the enzyme. In contrast, in quercetin this rigidity is changed into a B ring that is flexible and whose conformation does not allow good interaction in the active site, and this takes place before the quercetin can degrade to 3,4-dihydroxybenzoic acid, which according to the literature is a potent inhibitor of 15-sLOX [21][22][23] .…”

“…In other hand, some studies suggest a relationship between LOX inhibition and the ability of the inhibitors to reduce Fe 3+ in the active site 21 . In previous studies, the coumarins of H.multifolius showed very good antioxidant activity 15 .…”

“…In previous studies, the coumarins of H.multifolius showed very good antioxidant activity 15 . Therefore, compounds with antioxidant properties could be estimated to offer protection in rheumatic arthritis and other inflammatory diseases 21 and this would be better if the coumarins have phenolic hydroxyl or cathecol groups. D o c k i n g results showed that in the potent coumarin 2 the aliphatic hydroxyl is near of Fe 3 ·and create hydrogen bridges When carrying out docking with compounds 5 and 7 it was seen that both structures were located in the bonding site of arachidonic acid.…”

“…The structures of the compounds are shown in Figure 1: 1 7-O-prenyl-coumarin; 2 6-hydroxy-7-[(E,E)-3',7'-dimethyl-7'-hydroxy-2',5'-octodienyloxy] coumarin; 3 6-hydroxy-7-[(E,E)-3',7'-dimethyl-5'-hydroxy-2',6'-octodienyloxy] coumarin; 4 6-hydroxy-7-prenyl coumarin (prenyletin); 5 6,7-dihydroxy (esculetin); 6 7-hydroxy coumarin (umbelliferone; 7 6[β-D-glucopyrasyl]-7-hydroxy coumarin (esculin); 8 6,7 diacetyl-esculetin. The percent inhibition of all of them was compared with that of quercetin 9, a known LOX inhibitor 21 . The results besides show the importance of the presence of the catechol group in the aromatic systems or a location of hydroxyl groups in the geranyl chain .Their type and location accounts clearly for the value of % I of compound 2 compared to quercetin.…”