Synthesis of 3-Substituted Isocoumarins and Their Inhibitory Effects on Degranulation of RBL-2H3 Cells Induced by Antigen

Abstract

Eleven 3-substituted isocoumarins and a benzylidenephthalide were synthesized through thermal cyclization reaction of delta- and gamma-ketoamides, respectively. Subsequent deprotection of the hydroxyl groups of the resulting isocoumarin and benzylidenephthalide compounds afforded thunberginols A, B, and F, respectively, which originated from the processed leaves of Hydrangea macrophylla SERINGE var. thunbergii MAKINO. The synthesized isocoumarins and thunberginols were evaluated for their anti-allergic activity, in which thunberginol B exhibited the highest inhibitory potency on the degranulation of RBL-2H3 cells induced by antigen. Structure-activity relationship studies were carried out to determine the necessary substituents on the 3-phenylisocoumarin skeleton for inhibitory activity.

Structures of New Flavonoids and Benzofuran-Type Stilbene and Degranulation Inhibitors of Rat Basophilic Leukemia Cells from the Brazilian Herbal Medicine Cissus sicyoides

“…8 Resources Bank, Osaka, Japan) were evaluated using the method reported previously [37][38][39][40][41][42][43][44][45][46][47][48] with some modifications. Briefly, RBL-2H3 cells were dispensed into 48-well plates at a concentration of 4ϫ10 4 cells/well using Eagle's minimum essential medium (MEM, Sigma) containing fetal calf serum (10%), penicillin (100 units/ml), streptomycin (100 mg/ml), and 0.45 mg/ml of anti-dinitrophenyl (DNP) IgE.…”

“…[36][37][38] The glycosides (6-14, 16-22) were not subjected to the examination, since the glycoside moiety of flavonoids markedly reduces their activity in this in vitro bioassay method. 37) As a continuing study of the antiallergic constituents of natural medicines, [39][40][41][42][43][44][45][46][47][48] the effects of the principal constituents of C. sicyoides lacking a glycoside moiety on the release of b-hexosaminidase in RBL-2H3 cells were examined. As shown in Table 2, cissusin (4, IC 50 ϭ95 mM), kaempferol (5, 15 mM), quercetin (15, 3.3 mM), 7,3Ј,4Ј-trihydroxyflavone (23, 17 mM), tryptanthrin (33, ca.…”

Medicinal Flowers. XXXX.¹⁾ Structures of Dihydroisocoumarin Glycosides and Inhibitory Effects on Aldose Reducatase from the Flowers of <i>Hydrangea macrophylla</i> var. <i>thunbergii</i>

“…In the course of our chemical and pharmacological studies on Hydrangea plants [2][3][4][5][6][7][8] and medicinal flowers, [9][10][11][12][13][14] we recently reported the isolation and structure elucidation of secoiridoid glycosides named hydrangeamines A and B with a pyridine ring from the flowers of H. macrophylla var. thunbergii cultivated in Nagano prefecture, Japan.…”

“…Previously, we reported the isolation and structure determination of many chemical constituents with anti-diabetic, anti-allergic, and anti-bacterial activities from the processed leaves and the dried leaves of this plant. [2][3][4][5][6] However, a full chemical analysis of the flowers from this plant has not yet been performed. In the course of our chemical and pharmacological studies on Hydrangea plants [2][3][4][5][6][7][8] and medicinal flowers, [9][10][11][12][13][14] we recently reported the isolation and structure elucidation of secoiridoid glycosides named hydrangeamines A and B with a pyridine ring from the flowers of H. macrophylla var.…”

“…Furthermore, the inhibitory effects of the isolated compounds and its related compounds on aldose reductase were investigated. This paper deals with the structure elucidation of the new dihydroisocoumarin glycosides (1)(2)(3)(4)(5)(6) and the inhibitory effects of the constituents and their related compounds, acylated quinic acid analogs, on aldose reductase.…”