Co-reporter:Takashi Kikuchi, Yui Horii, Yukina Maekawa, Yuki Masumoto, Yasuko In, Koji Tomoo, Hiroyasu Sato, Akihito Yamano, Takeshi Yamada, and Reiko Tanaka
The Journal of Organic Chemistry October 6, 2017 Volume 82(Issue 19) pp:10611-10611
Publication Date(Web):August 31, 2017
DOI:10.1021/acs.joc.7b01259
Two novel 11(9 → 7)-abeo-ergostane-type steroids, named pleurocins A (1) and B (2), a 13,14-seco-13,14-epoxy ergostane, named eringiacetal B (3), and an ergostane steroid (4) were isolated from the fruiting bodies of Pleurotus eryngii (Pleurotaceae). Their structures were determined by spectroscopic data and X-ray crystallography. A possible biogenesis pathway for 1–3 was also described. Compounds 1–3 exhibited inhibitory activities against NO production with almost no cytotoxicity at concentrations lower than 30 μM.
Eringiacetal A, 5,6-seco-(5S,6R,7R,9S)-5,6:5,7:6,9-Triepoxyergosta-8(14),22-diene-3,7-diol, an Unusual Ergostane Sterol from the Fruiting Bodies of Pleurotus eryngii
Co-reporter:Takashi Kikuchi;Yuki Masumoto;Yasuko In;Koji Tomoo;Takeshi Yamada
European Journal of Organic Chemistry 2015 Volume 2015( Issue 21) pp:4645-4649
Publication Date(Web):
DOI:10.1002/ejoc.201500382
Abstract
A new rearranged ergostane-type steroid, named eringiacetal A (1), together with known compound 2, were isolated from the fruiting bodies of Pleurotus eryngii (Pleurotaceae). Its structure was fully elucidated by NMR spectroscopy and X-ray crystallography. Eringiacetal A (1) features an unprecedented 5,6-seco-(5S,6R,7R,9S)-5,6:5,7:6,9-triepoxyergosta-8(14),22-diene-3β,7β-diol. This is the first report of a 5,6-seco-ergostane-type steroid. A plausible biogenetic pathway of 1 from 2 is also described. Furthermore, isolated compounds were evaluated for inhibitory effects on nitric oxide (NO) production induced by lipopolysaccharide in macrophages. Compound 1 exhibited inhibitory activity on NO production (IC50 = 19.9 μM) accompanied by modest cytotoxicity (IC50 = 25.6 μM). Compound 2 did not have inhibitory effects on NO production or cytotoxicity (IC50 > 100 μM each).
Co-reporter:Takanobu Inoue, Yuuki Matsui, Takashi Kikuchi, Takeshi Yamada, Yasuko In, Osamu Muraoka, Chie Sakai, Kiyofumi Ninomiya, Toshio Morikawa, Reiko Tanaka
Tetrahedron 2015 Volume 71(Issue 18) pp:2753-2760
Publication Date(Web):6 May 2015
DOI:10.1016/j.tet.2015.03.017
Five novel phragmalin-type limonoids, carapanolides M–Q (1–5), together with two mexicanolide-type limonoids, carapanolides R–S (6–7), were isolated from the oil of Carapa guianensis AUBLET (Meliaceae) seeds, a traditional medicine in Brazil and Latin American countries. Their structures were elucidated on the basis of spectroscopic analyses using 1D and 2D NMR techniques and a single-crystal X-ray diffraction analysis. Compounds 1–7 along with 12 known limonoids, 8–19, isolated from the flower and seed oil of C. guianensis were assayed to determine their triglyceride metabolism-promoting activities in the high glucose-pretreated human hepatocellular carcinoma cell line, HepG2. Gedunin-type limonoid: 14 (% of control at 10 μM: 35.4±3.9), 13 (55.0±3.6 at 10 μM), and 18 (75.4±4.2 at 10 μM) significantly reduced TG levels in hepatocytes.
Co-reporter:Takashi Kikuchi, Aoi Ikedaya, Akiko Toda, Kenji Ikushima, Takahiro Yamakawa, Rina Okada, Takeshi Yamada, Reiko Tanaka
Phytochemistry Letters 2015 12() pp: 94-97
Publication Date(Web):
DOI:10.1016/j.phytol.2015.02.017
Co-reporter:Takanobu Inoue, Yuuki Matsui, Takashi Kikuchi, Yasuko In, Takeshi Yamada, Osamu Muraoka, Shunyo Matsunaga, and Reiko Tanaka
Organic Letters 2013 Volume 15(Issue 12) pp:3018-3021
Publication Date(Web):June 4, 2013
DOI:10.1021/ol400924u
Two novel limonoids, named guianolides A (1) and B (2), were isolated from the seeds of Carapa guianensis AUBLET (Meliaceae). Their structures were established by spectroscopic analyses and X-ray crystallography. Guianolides A (1) and B (2) featured an unprecedented carbon skeleton via the formation of a C-11–C-21 bond.
Co-reporter:Daisuke Saeki, Takeshi Yamada, Yasuko In, Tetsuya Kajimoto, Reiko Tanaka, Yota Iizuka, Takahisa Nakane, Akihito Takano, Kazuo Masuda
Tetrahedron 2013 69(5) pp: 1583-1589
Publication Date(Web):
DOI:10.1016/j.tet.2012.12.001
Co-reporter:Takanobu Inoue, Yumi Nagai, Aya Mitooka, Reina Ujike, Osamu Muraoka, Takeshi Yamada, Reiko Tanaka
Tetrahedron Letters 2012 Volume 53(Issue 49) pp:6685-6688
Publication Date(Web):5 December 2012
DOI:10.1016/j.tetlet.2012.09.108
Two novel limonoids, named carapanolides A (1) and B (2) were isolated from the seeds of Carapa guianensis AUBLET (Meliaceae), a traditional medicine in Brazil and Latin American countries. Their structures elucidated on the basis of spectroscopic analyses using 1D and 2D NMR techniques were quite unusual, bearing 2,9-oxygen bridge in the 9,10-seco-mexicanolide skeleton. Compound 1 showed moderate activity against L1210 cell line.
Co-reporter:Noriko Handa, Takeshi Yamada, Reiko Tanaka
Phytochemistry Letters 2012 Volume 5(Issue 3) pp:480-485
Publication Date(Web):September 2012
DOI:10.1016/j.phytol.2012.04.010
Four new lanostane-type triterpenoids, inonotsuoxodiol B (1), inonotsuoxodiol C (2), epoxyinonotsudiol (3), and methoxyinonotsutriol (4), were isolated from the sclerotia of Inonotus obliquus. Their structures were determined to be 3β,22R-dihydroxylanosta-9(11),24-dien-7-one (1), 3β,22R-dihydroxylanosta-7,24-dien-11-one (2), 9α,11α-epoxy-lanosta-7,24-diene-3β,22R-diol (3), and 7β-methoxylanosta-8,24-diene-3β,11α,22R-triol (4) on the basis of NMR spectroscopy, including 1D and 2D (1H–1H-COSY, NOESY, HMQC, HMBC) NMR spectra, and EIMS.Graphical abstractHighlights► New triterpenoids, 1–4 were isolated from the sclerotia of Inonotus obliquus. ► Structures of 1–4 were established by 2D NMR spectra and EIMS. ► 1 exhibited cytotoxic activity against all four cancer cell lines.
Co-reporter:Yuji Tanaka, Asami Sakamoto, Takanobu Inoue, Takeshi Yamada, Takashi Kikuchi, Tetsuya Kajimoto, Osamu Muraoka, Akira Sato, Yusuke Wataya, Hye-Sook Kim, Reiko Tanaka
Tetrahedron 2012 68(18) pp: 3669-3677
Publication Date(Web):
DOI:10.1016/j.tet.2011.12.076
Co-reporter:Reiko Tanaka, Hiroko Tsujii, Takeshi Yamada, Tetsuya Kajimoto, Harukuni Tokuda, Takanari Arai, Nobutaka Suzuki, Junya Hasegawa, Yoshio Hamashima, Manabu Node
European Journal of Medicinal Chemistry 2011 Volume 46(Issue 8) pp:3368-3375
Publication Date(Web):August 2011
DOI:10.1016/j.ejmech.2011.04.062
3α-Methoxyserrat-14-en-21β-ol (PJ-1) and 3β-methoxyserrat-14-en-21β-ol (PJ-2) were conjugated with well-known phenolic compounds, narigenin, hesperetin, genistein, and daidzein (1–8). Other conjugates of PJ-2–3,5-dihydroxy-4-methoxybenzoic acid (9), PJ-2–pyrogallol (10), and derivatives of PJ-1, PJ-2–3,3-dimethyl-succinates (11, 12), PJ-1, PJ-2–succinates (13, 14), PJ-2–glycine (15), PJ-2–piperidine acetic acid (16), and PJ-1 epoxy–3,3-dimethyl-succinate (17) were tested for their inhibitory effects on Epstein–Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). The inhibitory effects of 11 (IC50 = 251), 12 (IC50 = 248), and 17 (IC50 = 230 mol ratio/32 pmol/TPA), were 2-fold stronger than those of the other compounds such as oleanolic acid (IC50 = 449). Compounds 10, 11, and 17 inhibited mouse skin tumor promotion in an in vivo two-stage carcinogenesis model. The in vivo two-stage mouse-skin carcinogenesis test employed 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.Highlights► PJ-1 and PJ-2 were modified and coupled with natural occurring phenolics to afford novel conjugates (1–17). ► Compounds 11, 12, and 17 showed stronger inhibitory effects on EBV-EA than other conjugates, in vitro. ► Moreover, 10 and 11 potently inhibited mouse skin tumor promotion in in vivo two-stage carcinogenesis model using mouse-skin papillomas induced by DMBA/TPA.
Co-reporter:Reiko Tanaka, Misaki Toyoshima, Takeshi Yamada
Phytochemistry Letters 2011 Volume 4(Issue 3) pp:328-332
Publication Date(Web):September 2011
DOI:10.1016/j.phytol.2011.07.001
Two new lanostane-type triterpenoids, inonotsutriols D (1) and E (2), were isolated from the sclerotia of Inonotus obliquus (Pers.: Fr.) Pil. (Japanese name: kabanoanatake; Russian name: chaga). Their structures were determined to be lanost-8-ene-3β,22R,24R-triol (1) and lanost-8-ene-3β,22R,24S-triol (2) on the basis of spectral data, including 2D NMR analysis. In addition, major compounds, inotodiol (3), trametenolic acid (4), 3β-hydroxylanosta-8,24-dien-21-al (5), 21-hydroxylanosterol (6), inonotsuoxide A (7) and inonotsuoxide B (8) were identified, and all compounds, except 2, were evaluated for their cancer cell growth inhibitory activity against P388, HL-60, L1210 and KB cell lines.Graphical abstractNew triterpenoids named inonotsutriols D (1) and E (2) were isolated from I. obliquus. Their structures were determined as lanost-8-ene-3β,22R,24R-triol (1) and lanost-8-ene-3β,22R,24S-triol (2). Compound 1 exhibited cytotoxic activity against four cancer cell lines (P388, L1210, HL-60, and KB).Highlights► New triterpenoids, inonotsutriols D (1) and E (2) were isolated from I. obliquus. ► The structure of 1 was determined as lanost-8-ene-3β,22R,24R-triol. ► The structure of 2 was determined as lanost-8-ene-3β,22R,24S-triol. ► Cytotoxicities of compounds 1, 3–8 were examined using P388, L1210, HL-60, and KB cell lines. ► Compound 1 exhibited cytotoxic activity against all four cancer cell lines.
Co-reporter:Yuji Tanaka, Takeshi Yamada, Yasuko In, Osamu Muraoka, Tetsuya Kajimoto, Reiko Tanaka
Tetrahedron 2011 67(4) pp: 782-792
Publication Date(Web):
DOI:10.1016/j.tet.2010.11.028
Co-reporter:Hiroko Tsujii, Takeshi Yamada, Tetsuya Kajimoto, Reiko Tanaka, Harukuni Tokuda, Junya Hasegawa, Yoshio Hamashima, Manabu Node
European Journal of Medicinal Chemistry 2010 Volume 45(Issue 6) pp:2191-2197
Publication Date(Web):June 2010
DOI:10.1016/j.ejmech.2010.01.057
3α-Methoxyserrat-14-en-21β-ol (1) and 3β-methoxyserrat-14-en-21β-ol (2) and their conjugates with curcumin, kojic acid, quercetin, and baicalein (3–18), as well as new analogs (19–24) derived from 1 and 2, were tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). The inhibitory effects of 16 (IC50 = 330 mol ratio/32 pmol/TPA), 9 (IC50 = 335), 10 (IC50 = 338), and 15 (IC50 = 350) were stronger than those of the other compounds and the positive control, oleanolic acid (IC50 = 449). Compounds 15 and 16, which are conjugates of one molecule each of 1 or 2 and quercetin, inhibited mouse skin tumor promotion in an in vivo two-stage carcinogenesis model. The in vivo two-stage mouse skin carcinogenesis test employed 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.
Co-reporter:Noriko Handa, Takeshi Yamada, Reiko Tanaka
Phytochemistry 2010 Volume 71(14–15) pp:1774-1779
Publication Date(Web):October 2010
DOI:10.1016/j.phytochem.2010.07.005
An unusual lanostane-type triterpenoid, spiroinonotsuoxodiol (1), and two lanostane-type triterpenoids, inonotsudiol A (2) and inonotsuoxodiol A (3), were isolated from the sclerotia of Inonotus obliquus. Their structures were determined to be (3S,7S,9R)-3,7-dihydroxy-7(8 → 9)abeo-lanost-24-en-8-one (1), lanosta-8,24-dien-3β,11β-diol (2), and (22R)-3β,22-dihydroxylanosta-8,24-dien-11-one (3) on the basis of NMR spectroscopy, including 1D and 2D (1H–1H COSY, NOESY, HMQC, HMBC) NMR, and FABMS. Compounds 1–3 showed moderate activity against cultured P388, L1210, HL-60 and KB cells.The structure of a lanostane-type triterpenoid spiroinonotsuoxodiol was established as shown.
Co-reporter:Reiko Tanaka, Hiroko Tsujii, Takeshi Yamada, Tetsuya Kajimoto, Fumio Amano, Junya Hasegawa, Yoshio Hamashima, Manabu Node, Kayoko Katoh, Yutaka Takebe
Bioorganic & Medicinal Chemistry 2009 Volume 17(Issue 14) pp:5238-5246
Publication Date(Web):15 July 2009
DOI:10.1016/j.bmc.2009.05.049
Sixteen novel compounds; 3α-methoxyserrat-14-en-21β-ol (1) and 3β-methoxyserrat-14-en-21β-ol (2) and their curcumin, kojic acid, quercetin, and baicalein conjugates (3)–(18) were designed, synthesized, and evaluated for in vitro anti-HIV-1 reverse transcriptase (RT) activity in infected C8166-CCR5 cells, a human CD4+ T-lymphocyte cell line. Among them, kojic acid derivatives, 9–12 showed significant biological activity. In particular, the compound 13, the conjugate of two molecules of 3α-methoxyserrat-14-en-21β-ol (1) and one molecule of kojic acid, exerted significant anti-HIV activity with an EC50 value of 0.12 μg/mL.
Co-reporter:Chiharu Yamaguchi;Yasuko In;Shun-ichi Wada;Takeshi Yamada;Harukuni Tokuda
Chemistry & Biodiversity 2009 Volume 6( Issue 7) pp:1093-1100
Publication Date(Web):
DOI:10.1002/cbdv.200800266
Abstract
In search for cancer chemopreventive agents from natural sources, three oleanane- and four known lupane-type triterpenoids, and sitosterol from the stem bark of Betula ermanii were tested for their inhibitory effects on Epstein–Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Among them, 3β-acetoxy-12α-hydroxyoleanan-13β,28-olide (1) and 3β-acetoxy-11α,12α-epoxyoleanan-13β,28-olide (2) were investigated for the inhibitory effect in a two-stage carcinogenesis test on mouse skin using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter. 3β-Acetoxy-11α,12α-epoxyoleanan-13β,28-olide (2) was found to exhibit the potent antitumor promoting activity in the in vivo carcinogenesis test.
Co-reporter:Sayaka Taji, Takeshi Yamada, Shun-ichi Wada, Harukuni Tokuda, Kazuo Sakuma, Reiko Tanaka
European Journal of Medicinal Chemistry 2008 Volume 43(Issue 11) pp:2373-2379
Publication Date(Web):November 2008
DOI:10.1016/j.ejmech.2008.01.037
Two new lanostane-type triterpenoids, 1 and 2 besides two known lanostane-type triterpenoids, 3 and 4 were isolated from the sclerotia of Inonotus obliquus. Their structures were determined to be lanosta-8,23E-diene-3β,22R,25-triol (1) and lanosta-7:9(11),23E-triene-3β,22R,25-triol (2) by spectral data. These compounds were tested for their anti-tumor-promoting activity using a short-term in vitro assay for EBV–EA activation induced by TPA. Compounds 1, 2 and 4 were stronger than the positive control, oleanolic acid. The most abundant compound 4 was investigated for the inhibitory effect in a two-stage carcinogenesis test on mouse skin using DMBA as an initiator and TPA as a promoter. Compound 4 was found to exhibit the potent anti-tumor promoting activity in the in vivo carcinogenesis test.New triterpenoids 1 and 2 were isolated and their structures were determined to be 1 and 2. Compound 4 showed strong anti-tumor promoting activity in the in vivo carcinogenesis test.
Co-reporter:Sayaka Taji;Takeshi Yamada
Helvetica Chimica Acta 2008 Volume 91( Issue 8) pp:1513-1524
Publication Date(Web):
DOI:10.1002/hlca.200890165
Abstract
Three new lanostane-type triterpenoids, inonotsutriols A (1), B (2), and C (3) were isolated from the sclerotia of Inonotus obliquus (Pers.: Fr.) (Japanese name: kabanoanatake; Russian name: chaga). Their structures were determined to be (3β,21R,24S)-21,24-cyclolanost-8-ene-3,21,25-triol (1), (3β,21R,24R)-21,24-cyclolanost-8-ene-3,21,25-triol (2), and (3β,21R,24S)-21,24-cyclolanosta-7,9(11)-diene-3,21,25-triol (3) on the basis of NMR spectroscopy including 1D and 2D experiments (1H,1H-COSY, NOESY, HMQC, and HMBC) and EI-MS.
Co-reporter:Sayaka Taji;Takeshi Yamada;Shun-ichi Wada;Yasuko In;Yoshihide Usami;Kazuo Sakuma
Helvetica Chimica Acta 2007 Volume 90(Issue 11) pp:2047-2057
Publication Date(Web):16 NOV 2007
DOI:10.1002/hlca.200790214
Three new lanostane-type triterpenoids, inonotsulides A, B, and C (1–3, resp.) were isolated from the sclerotia of Inonotus obliquus (Pers.: Fr.) (Japanese name: Kabanoanatake; Russian name: Chaga). Their structures were determined to be (20R,24S)-3β,25-dihydroxylanost-8-en-20,24-olide (1), (20R,24R)-3β,25-dihydroxylanost-8-en-20,24-olide (2), and (20R,24S)-3β,25-dihydroxylanosta-7,9(11)-dien-20,24-olide (3) on the basis of chemical transformation, NMR spectroscopy including 1D and 2D (1H,1H-COSY, NOESY, HMQC, HMBC), EI-MS, and single-crystal X-ray analysis.
Co-reporter:Manabu Nishizawa;Takahiro Katoh;Harukuni Tokuda;Hironori Ohtsu;Masatoshi Takeo;Manabu Node
Chemistry & Biodiversity 2007 Volume 4(Issue 5) pp:1003-1007
Publication Date(Web):18 MAY 2007
DOI:10.1002/cbdv.200790068
(11E)-13-Oxo-15,16-dinorlabda-8(20),11-dien-19-oic Acid (1), obtained either from the stem bark of Thuja standishii or readily prepared in larger quantities from the related constituent 2, was found to significantly reduce the formation of papilloma in an in vivo two-stage mouse-skin-carcinogenesis model. Carcinogenesis was initiated by skin exposure to UV-B irradiation and promoted by topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA). Oral administration of 1, starting one week before and ending one week after irradiation, exhibited remarkable effects. First, papilloma formation started two weeks later than in the control group (lacking 1). Second, the average number of skin papilloma after 20 weeks was reduced by ca. 50% in the test group relative to the control.
Co-reporter:Toshifumi Minami;Harukuni Tokuda
Chemistry & Biodiversity 2006 Volume 3(Issue 7) pp:818-824
Publication Date(Web):26 JUL 2006
DOI:10.1002/cbdv.200690084
Ultraviolet light is the major cause of skin cancers in human, and several effects of ultraviolet light B (UVB) are thought to contribute to skin photocarcinogenesis. 3β-Methoxy-13α,14α-epoxyserratan-21β-ol (PJJ-34; 1) isolated from Picea jezoensisCarr. var. jezoensis showed the strongest antitumor-promoting activity among naturally occurring triterpenoids in the in vivo two-stage mouse skin-carcinogenesis test. To investigate the anti-initiating activity, we further studied mouse models initiated with ultraviolet-B (UVB) and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA). Oral administration of the PJJ-34 (1) during a period before and after the three times of UVB irradiation led to a remarkable effect: oral administration of a 0.0025% solution of 1 only to the test group, which started one week before and ended one week after the irradiation, showed less than half papillomas, and inhibition of tumor incidence and tumor multiplicity in comparison to the control group. Therefore, it was recognized that PJJ-34 (1) showed strong anti-initiating activity as well as anti-promoting activity. After all, 1 seems to be useful as cancer-chemopreventive agent.
Co-reporter:Kuniyoshi Sakai;Shunyo Matsunaga;Yuko Fukuda;Harukuni Tokuda
Chemistry & Biodiversity 2005 Volume 2(Issue 3) pp:421-428
Publication Date(Web):22 MAR 2005
DOI:10.1002/cbdv.200590021
In a search for cancer chemopreventive agents from natural sources, four lupane-type and seven oleanane-type triterpenoids, and ten synthetic analogs were screened as potential anti-tumor promoters by using the in vitro short-term 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Epstein–Barr virus early antigen (EBV-EA) activation assay. Among them, 25-acetoxy-3α-hydroxyolean-12-en-28-oic acid (1) and 3β,25-epoxy-3α-hydroxylup-20(29)-en-28-oic acid (2) were examined for anti-tumor promoting activity in a two-stage carcinogenesis assay on mouse skin with 7,12-dimethylbenz[a]anthracene (DMBA) and TPA as promoter. 25-Acetoxy-3α-hydroxyolean-12-en-28-oic acid (1) and 3β,25-epoxy-3α-hydroxylup-20(29)-en-28-oic acid (2) showed moderate inhibitory activities.
Co-reporter:Reiko Tanaka;Toshifumi Minami;Yohei Ishikawa;Harukuni Tokuda;Shunyo Matsunaga
Chemistry & Biodiversity 2004 Volume 1(Issue 6) pp:878-885
Publication Date(Web):24 JUN 2004
DOI:10.1002/cbdv.200490070
To search for cancer chemopreventive agents from natural sources, 13α,14α-epoxy-21α-methoxyserratan-3-one, 21α-methoxyserrat-13-en-3-one, and 21α-hydroxy-3β-methoxyserrat-14-en-30-al isolated from the cuticle of Picea jezoensis (Sieb.etZucc.) Carr.var. jezoensis (Pinaceae) were investigated for inhibitory effects in a two-stage mouse skin carcinogenesis test on mouse skin with 7,12-dimethylbenz[a]anthracene (DMBA) as initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as promoter. 21α-hydroxy-3β-methoxyserrat-14-en-30-al and 13α,14α-epoxy-21α-methoxyserratan-3-one were found to exhibit strong antitumor-promoting activities in the in vivo carcinogenesis test.
Co-reporter:Reiko Tanaka, Harukuni Tokuda, Yoichiro Ezaki
Phytomedicine (November 2008) Volume 15(Issue 11) pp:985-992
Publication Date(Web):1 November 2008
DOI:10.1016/j.phymed.2008.02.020
Natural resin acids present in rosin of Pinus spez., including isopimaric acid (1), mercusic acid (2), neoabietic acid (3), dehydroabietic acid (4), and podocarpic acid (8), as well as resin acid derivatives 8β,9α,13α-H-tetrahydroabietic acid (5), 8α,9α,13α-H-tetrahydroabietic acid (6), 13α-H-Δ8-dihydroabietic acid (7), maleopimaric acid (9), and fumaropimaric acid (10), were studied for their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Compounds 1, 3, 4, 7, and 10 (IC50: 352, 330, 311, 340, and 349, respectively) exhibited strong inhibitory effects compared to the other compounds. Among these, 1, 4, and 7 were selected to examine their effects on in vivo two-stage mouse skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA) as initiator and TPA as promoter. Treatment with compounds 4 and 7 (85 nmol) along with DMBA/TPA inhibited papilloma formation up to week 8 and the percentage of papilloma bearers in these two groups was approximately 80% at week 20. The average number of papillomas formed per mouse was 4.4 and 4.2 even at week 20 (p>0.05). Compounds 4 and 7 exhibited high activity in the in vivo anti-tumor-promoting test. In addition, rosin was examined in vivo for its chemopreventive effect. Treatment with rosin (50 μmol) along with DMBA (100 μg)/TPA (1 μg) inhibited papilloma formation up to week 8 and the percentage of papilloma bearers in this group was less than 80% at week 20. The average number of papillomas formed per mouse in the rosin-treated group was 3.8 even at week 20 (p>0.05). The in vivo two-stage mouse skin carcinogenesis test revealed that rosin possessed a pronounced anticarcinogenetic effect, and its high activity is due to the synergism of the diterpenes contained in it.
Co-reporter:Takashi Kikuchi, Aoi Ikedaya, Akiko Toda, Kenji Ikushima, Takahiro Yamakawa, Rina Okada, Takeshi Yamada, Reiko Tanaka
Phytochemistry Letters (June 2015) Volume 12() pp:94-97
Publication Date(Web):1 June 2015
DOI:10.1016/j.phytol.2015.02.017
•Three new compounds (1–3) were isolated from an extract of watermelon seeds.•1 and 2 were compounds with pyrrole and pyrazole rings in a molecule.•1–3 were evaluated for melanogenesis inhibitory activities.•1 exhibited modest inhibitory activity (inferior to arbutin) without cytotoxicity.Three new compounds, i.e. 1-[2-(5-hydroxymethyl-1H-pyrrole-2-carbaldehyde-1-yl)ethyl]-1H-pyrazole (1), 1-({[5-(α-d-galactopyranosyloxy)methyl]-1H-pyrrole-2-carbaldehyde-1-yl}-ethyl)-1H-pyrazole (2), and (4-hydroxyphenyl)methanol 4-[β-d-apiofuranosyl(1→2)-O-β-d-glucopyranoside] (3), were isolated from an extract of watermelon seeds. Compounds 1 and 2 were pyrazole-alkaloids with a pyrrole ring. This is the first study to show compounds with pyrrole and pyrazole rings in a molecule isolated from natural products. In the evaluation for melanogenesis inhibitory, compound 1 exhibited modest inhibitory activity on melanogenesis without cytotoxicity. Meanwhile compound 2 showed some inhibitory activity accompanied by some cytotoxicity.Download full-size image
![(5S,8R,9S,10S,11S,12Z)-8-benzoyl-2-(10,11-dihydroxy-12-hexenyl)-9-hydroxy-8-methoxy-3-methyl-1-oxa-7-azaspiro[4.4]non-2-ene-4,6-dione](http://img.cochemist.com/ccimg/1275600/1275589-07-5.png)
![(5S,8R,9S,10S,11S,12Z)-8-benzoyl-2-(10,11-dihydroxy-12-hexenyl)-9-hydroxy-8-methoxy-3-methyl-1-oxa-7-azaspiro[4.4]non-2-ene-4,6-dione](http://img.cochemist.com/ccimg/1275600/1275589-07-5_b.png)
![(5S,8S,9S,10S,11S,12Z)-8-benzoyl-2-(10,11-dihydroxy-12-hexenyl)-9-hydroxy-8-methoxy-3-methyl-1-oxa-7-azaspiro[4.4]non-2-ene-4,6-dione](http://img.cochemist.com/ccimg/1275600/1275589-06-4.png)
![(5S,8S,9S,10S,11S,12Z)-8-benzoyl-2-(10,11-dihydroxy-12-hexenyl)-9-hydroxy-8-methoxy-3-methyl-1-oxa-7-azaspiro[4.4]non-2-ene-4,6-dione](http://img.cochemist.com/ccimg/1275600/1275589-06-4_b.png)
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