76095-38-0Relevant academic research and scientific papers
Enzymatic studies of isoflavonoids as selective and potent inhibitors of human leukocyte 5-lipo-oxygenase
Mascayano, Carolina,Espinosa, Victoria,Sepúlveda-Boza, Silvia,Hoobler, Eric K.,Perry, Steve,Diaz, Giovanni,Holman, Theodore R.
, p. 894 - 901 (2015/06/23)
Continuing our search to find more potent and selective 5-LOX inhibitors, we present now the enzymatic evaluation of seventeen isoflavones (IR) and nine isoflavans (HIR), and their in vitro and in cellulo potency against human leukocyte 5-LOX. Of the 26 compounds tested, 10 isoflavones and 9 isoflavans possessed micromolar potency, but only three were selective against 5-LOX (IR-2, HIR-303, and HIR-309), with IC50 values at least 10 times lower than those of 12-LOX, 15-LOX-1, and 15-LOX-2. Of these three, IR-2 (6,7-dihydroxy-4-methoxy-isoflavone, known as texasin) was the most selective 5-LOX inhibitor, with over 80-fold potency difference compared with other isozymes; Steered Molecular Dynamics (SMD) studies supported these findings. The presence of the catechol group on ring A (6,7-dihydroxy versus 7,8-dihydroxy) correlated with their biological activity, but the reduction of ring C, converting the isoflavones to isoflavans, and the substituent positions on ring B did not affect their potency against 5-LOX. Two of the most potent/selective inhibitors (HIR-303 and HIR-309) were reductive inhibitors and were potent against 5-LOX in human whole blood, indicating that isoflavans can be potent and selective inhibitors against human leukocyte 5-LOX in vitro and in cellulo. Of the 26 compounds tested, 10 isoflavones and 9 isoflavans possessed micromolar potency, but only three were selective against 5-LOX (IR-2, HIR-303, and HIR-309), with IC50 values at least 10 times lower than those of 12-LOX, 15-LOX-1, and 15-LOX-2. Docking and steered molecular dynamics were performed to determinate the structure-activity relationship.
Synthesis and structure-activity relationship study of deoxybenzoins on relaxing effects of porcine coronary artery
Lu, Tzy-Ming,Kuo, Daih-Huang,Ko, Horng-Huey,Ng, Lean-Teik
experimental part, p. 10027 - 10032 (2011/05/17)
Deoxybenzoins are potent antioxidants and tyrosinase inhibitors with potential to be developed as food preservatives and cosmetic ingredients. To explore the potential in cardiovascular protection, 25 polyphenolic deoxybenzoins were synthesized and evaluated for inhibitory effects on KCl-induced porcine coronary arterial contraction. The results revealed deoxybenzoins are significant inhibitors of KCl-induced arterial contraction. Among those synthesized, two-thirds of the deoxybenzoins exhibited moderate to good efficacy on relaxing contracted artery including 2,4-dihydroxydeoxybenzoin with EC50 = 3.30 μM (Emax = 100%, n = 7) and 2,4-dihydroxy-4′-methoxydeoxybenzoin EC50 = 3.70 μM (E max = 100%, n = 5). Deoxybenzoins displayed an endothelium-dependent relaxing manner on the contracted artery; the contractile responses of neither endothelium denuded nor L-NAME deactivated rings were inhibited. The structure-activity relationships of deoxybenzoin on arterial relaxing effects concluded that the 2,4-dihydroxylated deoxybenzoins presented a potential vascular relaxing pharmacophore, with favoring substitution on ring B in the order of H ≤ p-OMe > p-OH > o-OMe > m,p-diOMe ≤ m-OMe.
Synthesis of various kinds of isoflavones, isoflavanes, and biphenyl- ketones and their 1,1-diphenyl-2-picrylhydrazyl radical-scavenging activities
Goto, Hideyuki,Terao, Yoshiyasu,Akai, Shuji
experimental part, p. 346 - 360 (2009/12/27)
Forty-eight kinds of isoflavones (8), thirty-one isoflavanes (9), and forty-seven biphenyl-ketones (10, 10') were synthesized from eleven kinds of substituted phenols (11) and six phenylacetic acids (12). Among them, seventy-five compounds are new. The radical scavenging activities of these compounds were evaluated using 1,1- diphenyl-2-picrylhydrazyl (DPPH) at pH 6.0. We found that thirty-nine out of forty-three compounds having a catechol moiety on either the A- or the B-ring exhibited a high activity (ED50=12-54 μM) similar to that of catechin. In these cases, the remaining part of their structure seemed to have little effect on their activity. Many 6- or 8-hydroxyisoflavanes (9E-I) and their biphenyl-ketone derivatives (10E-H) also showed a high activity (ED50=50=26-32 μM). This study suggests that natural isoflavones have the possibilities of exhibiting antioxidant activities through the hydroxylation at the C6-, C8-, or C3'-position or the formation of the isoflavanes (9) and/or the biphenyl-ketone derivatives (10') by metabolism or biotransformation.
Potential antioxidants and tyrosinase inhibitors from synthetic polyphenolic deoxybenzoins
Ng, Lean-Teik,Ko, Horng-Huey,Lu, Tzy-Ming
experimental part, p. 4360 - 4366 (2009/10/17)
Deoxybenzoins (DOBs) are one-pot synthetic precursors of isoflavones with feature analogous to those beneficial polyphenols such as resveratrol (stilbene) and phloretin (dihydrochalcone). In this study, seventeen polyphenolic DOBs were synthesized and evaluated by various antioxidant assays and tyrosinase inhibitory effect in vitro. Results displayed that these DOBs are powerful antioxidants; for example, 2,3,4-trihydroxy-3′,4′-dimethoxydeoxybenzoin possesses an excellent anti-lipid peroxidation activity (IC50 = 0.72 ± 0.16 μM), whilst 2,4,4′,5-tetrahydroxydeoxybenzoin showed good DPPH radical scavenging activity (IC50 = 0.69 ± 0.04 μM), which were better than Trolox and vitamin C. Besides exhibiting a weak metal chelating effect, these DOBs were effective in scavenging ABTS{radical dot}+ and superoxide anion (O2{radical dot} -) radicals. DOBs also exhibited potent mushroom tyrosinase inhibitory activity; for example 2,3,4′-trihydroxy-4-methoxydeoxybenzoin displayed stable and significant inhibitory effect on tyrosinase activity, with IC50 values 43.37, 43.10 and 46.10 μM at incubation intervals of 0.5, 1.5, and 2.5 h, respectively. These results suggest that, with the advantage of being readily synthesizable small molecules, DOBs can be potentially developed into clinical and industrial antioxidants. Crown Copyright
Structure-activity relationship studies of flavonoids as potent inhibitors of human platelet 12-hLO, reticulocyte 15-hLO-1, and prostate epithelial 15-hLO-2
Vasquez-Martinez, Yesseny,Ohri, Rachana V.,Kenyon, Victor,Holman, Theodore R.,Sepulveda-Boza, Silvia
, p. 7408 - 7425 (2008/09/18)
Human lipoxygenase (hLO) isozymes have been implicated in a number of disease states and have attracted much attention with respect to their inhibition. One class of inhibitors, the flavonoids, have been shown to be potent lipoxygenase inhibitors but their study has been restricted to those compounds found in nature, which have limited structural variability. We have therefore carried out a comprehensive study to determine the structural requirements for flavonoid potency and selectivity against platelet 12-hLO, reticulocyte 15-hLO-1, and prostate epithelial 15-hLO-2. We conclude from this study that catechols are essential for high potency, that isoflavones and isoflavanones tend to select against 12-hLO, that isoflavans tend to select against 15-hLO-1, but few flavonoids target 15-hLO-2.
Synthesis of Naturally Occuring 6,7-Dimethoxy-3',4'-methylenedioxyisoflavanone and its Analogues
Jain, Amolak C.,Prasad, Ashok K.
, p. 622 - 624 (2007/10/02)
6,7-Dimethoxy-3',4'-methylenedioxyisoflavanone (6a) isolated from the heartwood of Cordyla africana has now been synthesized by the Hoesch condensation of hydroxyquinol (1) with 3,4-methylenedioxybenzyl cyanide (2a) and partial methylation.The related iso
