New Pyrano-Pyrone from Goniothalamus tamirensis Enhances the Proliferation and Differentiation of Osteoblastic MC3T3-E1 Cells

Abstract

The genus Goniothalamus comprises about 160 species of shrubs and trees growing in tropical and subtropical Asia. 1) Many of these species are used for timber, as fiber sources, as mosquito repellant, and most interestingly in folk medicine in several countries. 2,3) Phytochemical studies of Goniothalamus species have led to the isolation and characterization of a large number of styryl-lactones. These can be classified into several main subtypes: styryl-pyrones, furano-pyrones, furano-furones, and pyrano-pyrones. 4) Styryl-lactones possess significant cytotoxic activity against several human tumor cell lines such as A-549 (lung carcinoma), HT-29 (colon adenocarcinoma), MCF-7 (breast carcinoma), RPMI (melanoma), U251 (brain carcinoma), 3,5) and to induce apoptosis in HL-60 leukemic cell. 6) Some of styryl-lactones have been synthesized via total synthesis. 3,7-10) Goniopypyrone, the first pyrano-pyrone compound, was first isolated in 1990 from G. giganteus. 11,12) It was high bioactive, showing ED 50 values of ca. 0.67 mg/ml in the cytotoxicity of human tumor cell lines (A-549, MCF-7, HT-29), high toxicity to the brine shrimp (BS), and significant inhibition of the formation of crown gall tumors on potato discs (PD). Typically, up to date, pyrano-pyrone compounds are found in some Goniothalamus species.The formation of bone involves a complex series of events, including the proliferation and differentiation of osteoprogenitor cells. Eventually, this results in the formation of a mineralized extracellular matrix. Most effective osteoporosis therapies reduce bone loss but do not restore lost bone mass and strength. Therefore, it is desirable to discover bone-building (anabolic) agents that stimulate new bone formation and correct the imbalance of microarchitecture characteristic of established osteoporosis. 13) As new bone formation is primarily a function of the osteoblasts, agents that regulate bone formation act either by increasing the proliferation of cells in the osteoblastic lineage or inducing osteoblast differentiation. 13,14) Early intervention is now possible with the help of some effective medications, which may reduce the risk of first and recurrent fractures.In our investigation of phytochemistry of the leaves of G. tamirensis, 9-deoxygoniopypyrone (2) and a new pyranopyrone, (ϩ)-8-epi-9-deoxygoniopypyrone (1), were isolated and identified using spectral methods. To investigate whether these compounds could stimulate the function of osteoblasts, their effects on cell growth, collagen content, alkaline phosphatase (ALP) activity, and calcium deposition were assessed in the pre-osteoblastic target cell line, MC3T3-E1, which is a well-characterized in vitro model of osteoblast differentiation. 15) Results and DiscussionCompound 1 Science and Technology; 18 Hoang Quoc Viet St., Caugiay, Hanoi, Vietnam: and c Faculty of Chemistry, Hanoi University of Science; 19 Le Thanh Tong St., Hoankiem, Hanoi, Vietnam. Received November 24, 2009; accepted January 8, 2010; published online January 19, 2010 The n...

Bioactive 6S-Styryllactone Constituents of Polyalthia parviflora

“…Tai et al reported the isolation of phenylpyranopyrones with a bicyclo structure and proposed three conformations, namely, the boat−boat, chair−chair, and boat−chair conformations ( Figure S2, Supporting Information). 15 Additionally, all styrylpyrones isolated from this plant were found to possess a 6S configuration, and their structural similarity suggested a common biogenetic pathway, which implies that the configuration of C-1 in 4−6 (originally C-6 in the isolated styrylpyrones) is S (Table S2, respectively. Thus, the absolute configuration of 4 was suggested as 1S,5S,7R,8R with 4a as the proposed structure ( Figure 3).…”

“…The 1 H and 13 C NMR data (Tables 1 and 2) of 4 were closely related to those of (+)-9-deoxygoniopypyrone. 13,15 However, the spectroscopic data of 5 and 6 were similar to those of 8-epi-9-deoxygoniopypyrone, 15 indicating that 4−6 are diastereomers with some structural differences. The data suggested that the equatorial proton (H-8) in 4 occurrs in an axial position in 5 and 6.…”

“…16 The other diastereomers, 5 and 6, were assigned as 1S,5S,7R,8S,3-endo,7-endo-(−)-8-epi-9-deoxygoniopypyrone and 1S,5S,7R,8S,3-exo,7-endo-(+)-8-epi-9-deoxygoniopypyrone, respectively. 15 Interestingly, it was found that the signs of specific rotation for all isolated 1S-phenylpyranopyrones (4−6) ( Table S2, Supporting Information) did not change upon altering the orientation of the 8-hydroxy group from axial (4: −49) to equatorial (5: −280); however, the absolute values changed dramatically. On the other hand, the data indicated that changing the direction of the 3-carbonyl group altered the sign of the specific rotation (Table S1, Supporting Information), with a 6S configuration, were similar to the reported data of (S)-goniothalamin, 17 (−)-ent-goniothalamin oxide, 18 (6S,7S,8S)-goniodiol, 19 and (−)-7-epi-goniodiol [(6S,7R,8S)-goniodiol], 20 respectively.…”

Styryl Lactones from Roots and Barks Goniothalamus lanceolatus

“…The coupling constant between H-5 and H-6 is 5.4 Hz, indicating that the dihedral angle is close to 45º, thus establishing H-5 is in equatorial orientation, leading to Rconfiguration. Based on the presented spectral data (Table 1) [3], (-)-ent-goniothalamin oxide 12 [3,7], Parvistone D 13 [3,6], 1S,5S,7R,8S,3-exo,7-endo-(+)-8-epi-9deoxygoniopypyrone 14 [3,8] and parvistone E 15 [3].…”

In vivo Antiplasmodial and Toxicological Effects of Goniothalamus lanceolatus Crude Extracts

“…The HPLC profile of the crude extract ( Figure 2) showed presence of the major component as well as several other minor constituents. From the mass data (Table 2), four more styryllactones were identified as 8-epi-9deoxygoniopypyrone 2 [13], 9-deoxygoniopypyrone 3 [14], digoniodiol 4 [15] and goniothalamin 5 [16]. Goniothalamin has been reported to possess antimalarial activity.…”