Structure and Stereochemistry of New Cytotoxic Clerodane Diterpenoids from the Bark of Casearia lucida from the Madagascar Rainforest

Prakash, C. V. S.; Hoch, Jeannine; Kingston, David G. I.

doi:10.1021/np010405c

Cited by 70 publications

(120 citation statements)

References 14 publications

(70 reference statements)

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“…10) The FAB-MS and 13 C-NMR spectra of 1 revealed its molecular weight as 518 and molecular formula C 29 H 42 O 8 . The UV spectrum showed absorption due to conjugated diene at l 225 nm.…”

Section: Resultsmentioning

confidence: 97%

“…13) The relative stereochemistry at the chiral centers was determined primarily through the NOESY spectrum as well as comparison with reported NMR data of analogous clerodane diterpenes. 1,10) The coupling constant of the signal at d 2.42 (1H, dd, Jϭ14.2, 2.4 Hz, H-10) suggested the b-axial orientation of H-10 while the NOE correlations between H-2/bH-10 proved that H-2 is b-oriented. On the other hand, NOE correlations between aH-8/aH-6, aH-6/aH-19, aH-19/aH-18 finalized the proposed structure of 1.…”

Section: Resultsmentioning

confidence: 99%

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Two New Cytotoxic Clerodane Diterpenoids from Casearia membranacea

Shen

Wang

et al. 2004

Chem. Pharm. Bull.

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Clerodanes are a group of novel diterpenoids with interesting biological effects such as antitumor-related activities. [1][2][3][4][5] Casearia membranacea HANCE (Flacourtiaceae) is the only species that belongs to the genus Casearia in Taiwan. 6) During the course of searching for novel antitumor agents from the terrestrial plants in Taiwan,[7][8][9] an ethanolic extract of the leaves and twigs of C. membranacea collected in Ken-ting showed significant cytotoxicity against the human prostate tumor cells (PC-3). To explore the origin of biological activity, bioassay-guided fractionation of the extract of the leaves and twigs of this species has resulted in the isolation of two new clerodane diterpenes, designated as caseamenbrols A (1) and B (2), together with the known casearlucin A (3). Herein, we wish to report the isolation, structural elucidation and cytotoxicity of these novel compounds. Results and DiscussionThe ethanolic extract of C. membranacea was fractionated by repeated column (Si gel and Sephadex LH-20) chromatography and preparative TLC to furnish caseamenbrols A (1, 0.012%) and B (2, 0.024%) in addition to casearlucin A (0.0023%).10)The FAB-MS and 13 C-NMR spectra of 1 revealed its molecular weight as 518 and molecular formula C 29 H 42 O 8 . The UV spectrum showed absorption due to conjugated diene at l 225 nm. The IR spectrum displayed absorption bands specific for a hydroxyl group (3445 cm -6). Taking into account three olefinic bonds and three ester carbonyls, the presence of three rings is justified to satisfy nine degrees of unsaturation. The spectral data of 1 are in conformity with the basic skeleton of clerodane diterpenes previously isolated from Casearia. 11,12) The presence of a six-carbon diene side chain at C-9 was confirmed by the long range correlations between H-12/C-9; H-14/C-12, C-13, C-16; H-15/C-13/C-14, C-16. In addition to casearlucin A (3), two new clerodane diterpenes, caseamembrols A (1) and B (2) have been isolated from the leaves and twigs of Casearia membranacea by bioassay-guided fractionation. The structures of the new compounds were established on the basis of extensive 1D-and 2D-NMR spectroscopic analysis. Compounds 1-3 exhibited significant cytotoxicity against human prostate (PC-3) cancer cells.

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“…10) The FAB-MS and 13 C-NMR spectra of 1 revealed its molecular weight as 518 and molecular formula C 29 H 42 O 8 . The UV spectrum showed absorption due to conjugated diene at l 225 nm.…”

Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Two New Cytotoxic Clerodane Diterpenoids from Casearia membranacea

Shen

Wang

et al. 2004

Chem. Pharm. Bull.

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“…It includes around 180 species that occur throughout the tropics and are widespread in the Americas, Africa, Asia, Malaysia, Australia and islands of the Pacific Ocean (1). At least 16 Casearia species have shown biological activity such as cytotoxic [C. arborea; C. grayi; C. grewiifolia; C. lucida; C. multinervosa; C. nigrescens; C. obliqua (2)(3)(4)(5)(6)(7)(8)]; antifungal [C. decandra (9)]; antidiabetic [C. esculenta (10)]; immunomodulatory [C. guianensis (11)]; antifertility [C. ilicifolia (12)]; antiophidian [C. mariquitensis (13)]; antitumor [C. membranacea (14)]; genotoxic [C. tomentosa (15)]; and antioxidant actions [C. velutina (16)]. The most studied among them is Casearia sylvestris Sw. that has shown several biological activities, including antitumor, antiulcer, analgesic, anti-inflammatory, cytotoxic, antifungal, anticancer, anti-snake and bee venom PLA 2 , genotoxic, trypanocidal, enzyme inhibitory, antihyperlipidemic and antibothropic properties (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27).…”

Section: Introductionmentioning

confidence: 99%

“…After 30 minutes, the absorbance of samples was read at 720 nm, considering a blank sample containing 15% sodium carbonate solution. The percentage of polyphenols (%) was determined from a standard curve (5,10,15,20,25,30,35, and 40 µg/mL) of pyrogallol (Sigma Chemical Co., USA). …”

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confidence: 99%

Bothrops jararacussu venom-induced neuromuscular blockade inhibited by Casearia gossypiosperma Briquet hydroalcoholic extract

Camargo¹,

Nazato²,

Silva³

et al. 2010

J. Venom. Anim. Toxins incl. Trop. Dis

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Abstract:The hydroalcoholic extract of Casearia gossypiosperma Briquet (Flacourtiaceae) was standardized for the first time through quality control procedures including pharmacognostic methods, fingerprint chromatograms, defined amounts of marker substances and physicochemical characteristics. The pharmacological activity of C. gossypiosperma (Cg) hydroalcoholic extract was assayed by a traditional in vitro test, which involved irreversible neuromuscular blockade induced by Bothrops jararacussu (Bjssu) venom (60 μg/mL) in mouse phrenic nerve-diaphragm preparations. Bjssu venom blocked muscle activity for 26 (± 2.0) minutes (n = 6). Cg extract (0.1 mg/mL) induced changes on the baseline muscle activity without impairing the muscle function and inhibited 87.6% (± 1.8) (n = 6) of the Bjssu venom-induced blockade. Both flavonoids (0.624 g%) and polyphenols (4.63 g%) from the extract were spectrophotometrically quantified. Therefore, the present study confirms the antibothropic activity of Cg extract, supporting the ethnomedical use of Casearia sp. in the treatment of snakebite victims.Key words: antibothropic extract, Bothrops jararacussu, Casearia gossypiosperma Briquet, snake venoms. pharmacologically assessed for the first time. Original PaPer The Journal of Venomous Animals and Toxins including Tropical DiseasesIn vivo myotoxic effects and in vitro irreversible neuromuscular blockade effects of crude venom from the snake Bothrops jararacussu are well known pharmacological methods used to study drugs showing antivenom properties (29,30). Thus, the aim of the present study was to verify the capability of Casearia gossypiosperma hydroalcoholic extract to neutralize the neuromuscular blockade induced by Bothrops jararacussu venom. MATERIALS AND METHODS Plant Material and ExtractionLeaves from an adult C. gossypiosperma Briquet (Cg) tree were collected from the herbarium at the Higher School of Agriculture Luiz de Queiroz (ESALQ) of the University of São Paulo, Piracicaba, São Paulo, Brazil, in January 2006; the species was previously identified in 1988 (protocol IAC 38115). Cg leaves were dried at 35°C to 40°C for 24 hours. The dried leaves were then powdered, ground in a mill, macerated (200 g, during five days) in 2 L of 70% ethanol and the suspension was percolated (under protection against light) at 20 drops/minute, resulting in a 10% (m/v) hydroalcoholic extract. Quality Control Assays of the Medicinal Plants Ash and humidity testsTo observe elementary physical and chemical characteristics, Cg powder was subjected to ash and humidity tests (31). Briefly, 100 g of the specimen powder were placed in six calibrated melting pots, which were warmed until total carbonization of the powders. The melting pots were kept at 650°C and the ashes were then weighed. Results are expressed as grams of ashes/100 g of sample. The humidity test was performed by placing 1 g of specimen powder in six calibrated porcelain capsules, which were heated at 105ºC during four hours and then weighed. Thin Layer Chromatography (TLC)Aliquots...

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“…(Beutler et al 2000), C. lucida Tul. (Prakash et al 2002), C. sylvestris (Oberlies et al 2002) e C. tremula (Griseb.) C. Wright (Gibbons et al 1996) indicaram que os compostos ativos presentes nos extratos alcoólicos são diterpenos, chamados de casearinas; entretanto não se conhece o sítio de secreção e/ou armazenamento destes compostos lipídicos.…”

Section: Introductionunclassified

Anatomia e histoquímica das estruturas secretoras da folha de Casearia decandra Jacq. (Salicaceae)

Thadeo¹,

Meira²,

Azevedo³

et al. 2009

Rev. bras. Bot.

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-(Anatomy and histochemistry of secretory structures from the leaf of Casearia decandra Jacq. (Salicaceae)). Extensive investigations have emphasized the therapeutic properties of Casearia species related with compounds secreted by specialized structures in the leaves. Therefore, the objective of this study was to characterize anatomical and histochemically the secretory structures present in leaves of C. decandra. Material was collected from natural populations of Mata da Biologia (Zona da Mata of Minas Gerais State, municipality of Viçosa). Leaves were fixed in FAA and subjected to usual methodology to obtain permanent slides. The sections were stained with toluidine blue pH 4 for structural characterization, with xylidine ponceau for total protein and PAS for neutral polysaccharides. The other histochemical tests were applied to transversally and longitudinally sectioned fresh samples. The secretory system of C. decandra consists of ducts and cavities dispersed on the leaf lamina and petiole and idioblasts present in the vascular tissues, cortical parenchyma of the midrib and in the palisade parenchyma. The ducts are distributed in the cortical parenchyma of the rib and continue in this same region of the petiole. In the mesophyll there are numerous cavities in the subepidermic layer or distributed in the interface between the palisade and spongy parenchyma. Lipophilic and hydrophilic substances were detected, confirming oil-resin lipids within ducts and cavities, and phenolic compounds, of the tannin type, within idioblasts and parenchyma. Alkaloids, polysaccharides and proteins were not detected as secretory products. This work reported the presence of ducts and cavities for the genus Casearia. Histochemical tests confirm the secretory product complexity, besides indicating fundamental tissues such as sites of synthesis and/or accumulation of phenolic compounds.Key words -cavity, ducts, Flacourtiaceae, idioblasts, secretory structures RESUMO -(Anatomia e histoquímica das estruturas secretoras da folha de Casearia decandra Jacq. (Salicaceae)). Extensivas investigações têm enfatizado as propriedades terapêuticas das espécies de Casearia, propriedades estas relacionadas com compostos secretados por estruturas especializadas presentes nas folhas. Portanto, objetivou-se caracterizar anatômica e histoquimicamente as estruturas secretoras presentes nas folhas de C. decandra. O material foi coletado em populações naturais da Mata da Biologia (Zona da Mata de MG -Viçosa). As folhas foram fixadas em FAA em etanol 50% e processadas conforme metodologia usual para obtenção de laminário permanente, sendo as seções coradas com azul de toluidina pH 4,0 para caracterização estrutural, com ponceau de xilidina para proteínas totais e PAS para polissacarídeos neutros. Os demais testes histoquímicos foram aplicados a amostras frescas seccionadas transversal e longitudinalmente. O sistema secretor de C. decandra é composto por ductos e cavidades dispersos pela lâmina foliar e pecíolo, e por idioblastos presentes nos te...

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Structure and Stereochemistry of New Cytotoxic Clerodane Diterpenoids from the Bark of Casearia lucida from the Madagascar Rainforest

Cited by 70 publications

References 14 publications

Two New Cytotoxic Clerodane Diterpenoids from Casearia membranacea

Two New Cytotoxic Clerodane Diterpenoids from Casearia membranacea

Bothrops jararacussu venom-induced neuromuscular blockade inhibited by Casearia gossypiosperma Briquet hydroalcoholic extract

Anatomia e histoquímica das estruturas secretoras da folha de Casearia decandra Jacq. (Salicaceae)

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