Antiproliferative Prenylated Stilbenes and Flavonoids from Macaranga alnifolia from the Madagascar Rainforest^,1

Abstract

Bioassay-guided fractionation of an extract of the fruit of Macaranga alnifolia from Madagascar led to the isolation of four new prenylated stilbenes, schweinfurthins E-H (1-4), and one new geranylated dihydroflavonol, alnifoliol (5). The known prenylated stilbene, vedelianin (6), and the known geranylated flavonoids, bonanniol A (7), diplacol (8), bonannione A (9) and diplacone (10), were also isolated. All ten compounds were tested for antiproliferative activity in the A2780 human ovarian cancer cell line assay. Vedelianin (IC 50 = 0.13 µM) exhibited the greatest activity among all isolates, while schweinfurthin E (IC 50 = 0.26 µM) was the most potent of the new compounds.The genus Macaranga is a large genus of the Euphorbiaceae family. Observation of Macaranga plants in their natural environment has revealed that they produce thread-like wax crystals on their ste ms, which make the slippery surfaces impassable for all insects except a species of ants known as "wax runners". Chemical analysis has indicated that terpenoids make up a majority of the wax bloom content that helps maintain this symbiotic relationship between plant and insect. 2 One of the more commonly studied species of this genus is M. tanarius, noted for its diterpenoid 3,4 and flavonoid 5-7 content. Work has also been performed on the isolation and characterization of terpenes from M. carolinensis ,8 flavonoids from M. conifera 9 and M. denticulate ,10 chromenoflavones from M. indica , 11 clerodane diterpenes from M. monandra , 12 bergenin derivatives and polyphenols from M. peltata , 13 , 14 prenylflavones from M. pleiostemona , 15 a geranyl flavanone from M. schweinfurthii ,16 tannins from M. sinensis ,17 a rotenoid and other compounds from M. triloba , 18 and a geranylflavonol from M. vedeliana. 19 No phytochemical studies have been previously reported for M. alnifolia.

Anti-Helicobacter pyloriand Thrombin Inhibitory Components from Chinese Dragon’s Blood,Dracaena cochinchinensis

“…After removing the solvent, the aqueous residue was partitioned in sequence with CHCl 3 and n-BuOH, yielding CHCl 3 and n-BuOH extracts. The two fractions were subjected to a series of chromatographic steps to afford eight new flavonoid derivatives (1-8) and 14 known compounds (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22).…”

“…The UV absorption at 328 nm was characteristic of a stilbene skeleton. 18 Its IR spectrum displayed the presence of aromatic rings (1606, 1510, and 1466 cm -1 ) and hydroxy functions (3406 cm -1 13 C NMR data of 2 revealed that 2 was similar to 1 except that two meta-coupled doublets at δ 6.33 and 6.56 (1H, d, 1.8, each) could be observed in 2, in place of the symmetrical aromatic proton pattern at δ 6.69 (2H, s)] in 1, suggesting also a stilbene moiety and a deoxotetrahydrochalcone unit in the structure of 2. The complete assignment of the protonated carbon resonances was made using the HSQC spectrum, while analysis of the HMBC and ROESY spectra of 2 confirmed the existence of a stilbene moiety and a deoxotetrahydrochalcone unit in the structure of 2 ( Figure 2).…”

“…Briefly, Mueller-Hinton agar (Oxoid, Basingstoke, UK) plates (10 mL/ each) were prepared containing 7% lysed sheep blood (Shanghai Kunbo Trading Co., Ltd., China) and 2-fold serial dilutions of the test compounds. They were inoculated with 5 µL of each bacterial (11) 31.3 7-hydroxy-3-(4-hydroxybenzyl)-8-methoxychroman (12) 55.9 (2S)-4′,5-dihydroxy-7-methoxy-8-methylflavan (13) 55.9 4,4′,6-trihydroxy-2-methoxydihydrochalcone (14) 111.1 4,4′-dihydroxy-2′-methoxychalcone (15) 118.5 (-)-7-hydroxy-4′-methoxyflavan (16) 250.0 4,4′-dihydroxy-2-methoxydihydrochalcone (17) 235.3 trans-3,5-dihydroxy-4′-methoxystilbene (18) 264.5 4′-hydroxy-2,4-dimethoxydihydrochalcone (19) 223.8 trans-3,4′,5-trihydroxystilbene (20) 280.7 2,4,4′-trihydroxydihydrochalcone (21) 248.1 4,4′-dihydroxy-2, 6-dimethoxydihydrochalcone (22) 211.9 amoxycillin a 0.08 metronidazole a 747.7 a Amoxycillin and metronidazole were used as positive controls. suspension (10 7 cfu/mL) using a multipoint inoculator (Sakuma, Tokyo, Japan) and incubated at 37°C for 3 days under a microaerobic atmosphere in an incubator consisting of 5% O 2, 10% CO2, and 85% N 2 with 98% humidity (Napco Co., Winchester, VA).…”

Phytochemistry and pharmacology of the genus Macaranga: A review

“…In folk medicine, traditional healers use fresh or dried leaves of some Macaranga species to treat swellings, cuts, sores, boils and bruises (Nick et al, 1995). A phytochemical review of literatures indicates the genus Macaranga to be a rich source of the isoprenylated, geranylated and farnesylated flavonoids (Schutz et al, 1995;Jang et al, 2002;Phormmart et al, 2005;Kawakami et al, 2008;Thanh et al, 2012) and stilbenes (Beutler et al, 1998;Yoder et al, 2007;Thanh et al, 2012). Furthermore, more classes of secondary metabolites like terpenes (Salah et al, 2003;Jang et al, 2004;Phormmart et al, 2005;Kawakami et al, 2008), tannins (Lin et al, 1990;Gunawan-Puteri and Kawabata, 2010;Ngoumfo et al, 2008), coumarins (Sutthivaiyakit et al, 2002;Darmawan et al, 2012) and other types of compounds (Ramaiah et al, 1979;Ngoumfo et al, 2008;Matsunami et al, 2009;Zakaria et al, 2010) are known to be isolated from different species of the genus Macaranga.…”

“…An increasing number of phytochemical studies are being carried out on plants belonging to the genus Macaranga due to their various traditional uses. Thus, the isolated natural products from this genus have been reported to display interesting biological activities including antitumor (Kaaden et al, 2001;Yoder et al, 2007;Zakaria et al, 2012), antioxidant (Sutthivaiyakit et al, 2002;Phormmart et al, 2005;Matsunami et al, 2009), antimicrobial (Salah et al, 2003;Lim et al, 2009) and anti-inflammatory (Jang, et al, 2002). This is a resourceful area of research as many species of Macaranga are used in traditional medicine as well as exhibits various pharmacological properties while their chemistry indicates varied chemical structures.…”