Chalcones from Angelica keiskei: Evaluation of Their Heat Shock Protein Inducing Activities

Abstract

Five new chalcones, 4,2',4'-trihydroxy-3'-[(2E,5E)-7-methoxy-3,7-dimethyl-2,5-octadienyl]chalcone (1), (±)-4,2',4'-trihydroxy-3'-[(2E)-6-hydroxy-7-methoxy-3,7-dimethyl-2-octenyl]chalcone (2), 4,2',4'-trihydroxy-3'-[(2E)-3-methyl-5-(1,3-dioxolan-2-yl)-2-pentenyl]chalcone (3), 2',3'-furano-4-hydroxy-4'-methoxychalcone (4), and (±)-4-hydroxy-2',3'-(2,3-dihydro-2-methoxyfurano)-4'-methoxychalcone (5), were isolated from the aerial parts of Angelica keiskei Koidzumi together with eight known chalcones, 6-13, which were identified as (±)-4,2',4'-trihydroxy-3'-[(6E)-2-hydroxy-7-methyl-3-methylene-6-octenyl]chalcone (6), xanthoangelol (7), xanthoangelol F (8), xanthoangelol G (9), 4-hydroxyderricin (10), xanthoangelol D (11), xanthoangelol E (12), and xanthoangelol H (13), respectively. Chalcones 1-13 were evaluated for their promoter activity on heat shock protein 25 (hsp25, murine form of human hsp27). Compounds 1 and 6 activated the hsp25 promoter by 21.9- and 29.2-fold of untreated control at 10 μM, respectively. Further protein expression patterns of heat shock factor 1 (HSF1), HSP70, and HSP27 by 1 and 6 were examined. Compound 6 increased the expression of HSF1, HSP70, and HSP27 by 4.3-, 1.5-, and 4.6-fold of untreated control, respectively, without any significant cellular cytotoxicities, whereas 1 did not induce any expression of these proteins. As a result, 6 seems to be a prospective HSP inducer.

Three New Chalcones from the Aerial Parts of Angelica keiskei

“…Its molecular formula was established as C 25 H 28 O 6 by the HR‐ESI‐MS ( m / z 425.1964 ([ M + H] + )). The 1 H‐ and 13 C‐NMR spectra of 3 ( Tables and ) also showed the typical signals for the 3′‐substituted chalcone as those of 1 and 2 . Three CH 2 group appeared at δ (H) 3.30 ( d , J = 16.6, H a –C(1′′)) and 2.80 ( d , J = 16.6, H b –C(1′′))/ δ (C) 29.1 (C(1′′)), 1.93 – 1.96 ( m , H a –C(4′′)) and 1.61 – 1.63 ( m , H b –C(4′′))/36.0 (C(4′′)), and 1.94 – 1.98 ( m , H a –C(5′′)) and 1.60 – 1.63 ( m , H b –C(5′′))/27.5 (C(5′′)), a CH group at δ (H) 3.37 (br.…”

“…Compound 2 was obtained as a yellow solid and its molecular formula was determined as C 25 H 28 O 5 by the HR‐ESI‐MS analysis ( m / z 409.2008, [ M + H] + ). The 1 H‐ and 13 C‐NMR spectra of 2 ( Tables and ) exhibited characteristics of the 3′‐substituted chalcone, as found for 1 . In its 1 H‐ and 13 C‐NMR spectra, an oxygenated CH group was observed at δ (H) 3.43 ( dd , J = 8.2, 3.8, H–C(4′′))/ δ (C) 77.7 (C(4′′)), three CH 2 groups at δ (H) 3.13 ( dd , J = 13.4, 11.3, H α –C(1′′)) and 2.80 ( dd , J = 13.4, 3.7, H β –C(1′′))/ δ (C) 22.1 (C(1′′)), 2.52 ( ddd , J = 12.8, 7.2, 5.4, H ax –C(6′′)) and 1.93 ( m , H eq –C(6′′))/32.7 (C(6′′)), and 1.76 – 1.84 ( m , H a –C(5′′)) and 1.52 – 1.63 ( m , H b –C(5′′))/32.9 (C(5′′)), a CH group at δ (H) 2.57 ( dd , J = 11.3, 3.7, H–C(2′′))/ δ (C) 51.4 (C(2′′)), and two Me groups at δ (H) 1.06 ( s , 3 H)/ δ (C) 27.1 (C(10′′)) and 0.96 ( s , 3 H)/18.2 (C(9′′)).…”

“…Compound 1 was isolated as a yellow solid and exhibited a protonated molecular ion peak at m / z 329.1020 ([ M + H] + ) in the HR‐ESI‐MS, consistent with the molecular formula C 18 H 16 O 6 . The 1 H‐ and 13 C‐NMR spectra of 1 ( Tables and ) showed signals for a chalcone skeleton at δ (H) 7.63 ( d , J = 8.8, H–C(2,6))/ δ (C) 131.9 (C(2,6)), 6.85 ( d , J = 8.8, H–C(3,5))/117.0 (C(3,5)), 7.67 ( d , J = 15.2, H–C( α ))/118.7 (C( α )), 7.80 ( d , J = 15.2, H–C( β ))/145.6 (C( β )), 6.64 ( d , J = 9.2, H–C(5′))/103.4 (C(5′)), 8.03 ( d , J = 9.2, H–C(6′))/131.4 (C(6′)), and δ (C) 194.2 (C=O) . In the 1 H‐NMR spectrum, a CH 2 group was observed as a broad singlet at low field, δ (H) 3.58 (CH 2 (1′′)).…”

Chalcone: A Privileged Structure in Medicinal Chemistry

“…Such a reaction requires reflux at an elevated temperature or takes a longer time at room temperature. 55,56,99 However, with a nucleophile substitution on the α -position, mild conditions are generally sufficient (Table 2, entry 3). 100 …”

Regulation of the mammalian heat shock factor 1

“…Another aromatic phytochemical, the chalcone derivative (±)‐4,2′,4′‐trihydroxy‐3′‐[(6E)‐2‐hydroxy‐7‐methyl‐3‐methylene‐6‐octenyl]chalcone (Fig. ), was also reported to activate HSF1‐dependent transcription in human lung cancer NCI‐H460 cells . In an effort towards identification of Hsp‐inducing agents from natural products, this chalcone was isolated from the areal parts of Angelica keiskei Koidzumi (Umbelliferae), an edible plant that is considered as a health food in Korea and Japan .…”