Pentacyclic Research Articles

Rapid assembly of the procyanidin A skeleton

Arylpropynals and two equivalents of phloroglucinol react to produce pentacyclic ketals. In addition, 4-methoxydibromocinnamaldehyde also reacted to form procyanidin A-skeleton.

Oleanolic Acid Alters Multiple Cell Signaling Pathways: Implication in Cancer Prevention and Therapy.

Nowadays, much attention has been paid to diet and dietary supplements as a cost-effective therapeutic strategy for prevention and treatment of a myriad of chronic and degenerative diseases. Rapidly accumulating scientific evidence achieved through high-throughput technologies has greatly expanded the understanding about the multifaceted nature of cancer. Increasingly, it is being realized that deregulation of spatio-temporally controlled intracellular signaling cascades plays a contributory role in the onset and progression of cancer. Therefore, targeting regulators of oncogenic signaling cascades is essential to prevent and treat cancer. A plethora of preclinical and epidemiological evidences showed promising role of phytochemicals against several types of cancer. Oleanolic acid, a common pentacyclic triterpenoid, is mainly found in olive oil, as well as several plant species. It is a potent inhibitor of cellular inflammatory process and a well-known inducer of phase 2 xenobiotic biotransformation enzymes. Main molecular mechanisms underlying anticancer effects of oleanolic acid are mediated by caspases, 5′ adenosine monophosphate-activated protein kinase, extracellular signal–regulated kinase 1/2, matrix metalloproteinases, pro-apoptotic Bax and bid, phosphatidylinositide 3-kinase/Akt1/mechanistic target of rapamycin, reactive oxygen species/apoptosis signal-regulating kinase 1/p38 mitogen-activated protein kinase, nuclear factor-κB, cluster of differentiation 1, CKD4, s6k, signal transducer and activator of transcription 3, as well as aforementioned signaling pathways . In this work, we critically review the scientific literature on the molecular targets of oleanolic acid implicated in the prevention and treatment of several types of cancer. We also discuss chemical aspects, natural sources, bioavailability, and safety of this bioactive phytochemical.

Pentacyclic Guanidine Alkaloids from Far Eastern Sponge Monanchora Ulchra – Inhibitors of O-Glycosyl Hydrolases of Marine Macro- and Micro-organisms

Pentacyclic Guanidine Alkaloids from Far Eastern Sponge Monanchora Ulchra – Inhibitors of O-Glycosyl Hydrolases of Marine Macro- and Micro-organisms

New pentacyclic triterpene ester and flavone glycoside from the biologically active extract of Carduus pycnocephalus L.

Bioassay guided phytochemical investigation of petroleum ether, chloroform and butanol fractions obtained from biologically active total alcoholic extract of Carduus pycnocephalus led to isolation of two new compounds, 3-O-acetyl-ursolic acid-28-ethyl ester (compound 1) and diosmetin-7-O-α-L-arabinopyransyl (1```→4``)-β-D- glucopyranoside (compound 5) along with three known compounds, bis (2-ethylhexyl) benzene-1,2-dicarboxylate) (compound 2), 3α, 24 dihydroxyolean-12-en-28, 30-dioic acid dimethyl ester (compound 3) and kaempferol (compound 4). Their structures were established on the basis of spectroscopic methods (UV, MS, 1H NMR, 13C NMR, COSY, HSQC and HMBC) and by comparison with published data. Compounds 2 and 3 were isolated for the first time from genus Carduus. The cytotoxic, antioxidant, and antimicrobial activities of the ethanolic extract were evaluated and the extract showed variable degrees of activities. It showed significant cytotoxic activity against MCF-7, A-549 and HepG-2 cell lines with IC50, 17.9, 17.5 and 21.8 µg, respectively. The extract displayed weak antioxidant activity by scavenging of DPPH with SC50 554.2 µg. In agar diffusion assay, the extract exhibited strong antibacterial activities against Gram negative bacteria Pseudomonas aeruginosa and Escherichia coli and strong antifungal activity against Syncephalastrum racemosum. Key words: Carduus pycnocephalus L.; new triterpene ester, flavonoidal glycoside, antioxidant, cytotoxic, antimicrobial activity.

Effect of betulinic acid preconditioning on oxidative stress response during cerebral ischemia-reperfusion in mice

Objective To evaluate the effects of betulinic acid preconditioning on oxidative stress response during cerebral ischemia-reperfusion (I/R) in mice.Methods Seventy-two male Kunming mice,aged 3 months,weighing 25-35 g,were randomly divided into 3 groups (n =24 each) using a random number table:sham operation group (group S),I/R group,and betulinic acid preconditioning group (group BP).Cerebral I/R was induced by middle cerebral artery occlusion in mice anesthetized with 10％ chloral hydrate 40 ml/kg.In group BP,betulinic acid 50 mg/kg was administered by intragastric gavage everyday for 7 days before ischemia,while the equal volume of solvent dimethyl sulfoxide was given in S and I/R groups.At 22 h of reperfusion,neurological function was assessed and scored.The mice were then sacrificed and brains were removed for determination of infarct size,expression of NADPH oxidase (Nox1,Nox2 and Nox4) and p22phox mRNA,activity of ROS and apoptosis rate in the infarcted zone.Results Compared with S group,neurological score,cerebral infarct size,activity of ROS and apoptosis rate in the infarcted zone were significantly increased,and the expression of Nox1,Nox2,Nox4 and p22phox mRNA was up-regulated in group I/R.Compared with group I/R,neurological score,cerebral infarct size,activity of ROS and apoptosis rate in the infarcted zone were significantly decreased,and the expression of Nox1,Nox2,Nox4 and p22phox mRNA was down-regulated in group BP.Conclusion Betulinic acid preconditioning mitigates cerebral I/R injury through inhibiting oxidative stress response in mice. Key words: Pentacyclic triterpenes; Ischemic preconditioning; Brain; Reperfusion injury; Oxidative stress

Anti-tumor mechanisms of oleanolic acid

Oleanolic acid (OA),a pentacyclic triterpenoid,possesses a variety of pharmacological activities,such as hepatoprotective effect,anti-inflammatory,enhancing immunity.Recently,many studies show that OA has inhibitory effects on the growth of many tumors and is a kind of potential anti-tumor drug.Itsanti-tumor mechanisms mainly include regulating signaling pathway,arresting cell cycle,inducing apoptosis,anti-angiogenesis,inhibiting tumor invasion and so on. Key words: Oleanolic acid; Antineoplastic agents; Apoptosis

A pentacyclic triterpene from the leaves of Combretum collinum Fresen showing antibacterial properties against Staphylococcus aureus

Leaf extracts of six different plants, many of which are used by traditional healers, were screened for antibacterial activity. These include Adina microcephaha, Combretum aurea,Combretum bracteosam, Combretum collinum, Filicium decipiens and Ficus moraceae. The highest mass of 118 mg was extracted with acetone from F. decipiens and the lowest mass of 18 mg was extracted from F. moraceae. The bioautography showed antibacterial activity of the dichloromethane and acetone extracts of C. collinum subspecies suluense and F. decipiensagainst Escherichia coli. It also showed antibacterial activity of the acetone extract of C. collinumsubspecies suluense against Staphylococcus aureus. Two compounds were isolated from these extracts and characterized. Their minimum inhibitory concentrations were determined. One compound from C. collinum subspecies suluense had MIC value of 0.5689 mg/ml and compound E had 1.479 mg/ml. The chemical structure proposed for the compound was determined by correlation of HNMR and GC-MS data. The chemical structure of the other compound was not proposed. Key words: Combretum collinum subspecie suluense, acetone extracts.

Synthesis, characterization and neuropharmacological activity of novel angular pentacyclic phenothiazine

13H-5,14-dihydroquinoxalino[2,3-a]phenothiazine (a new pentacyclic ring system) was synthesized by condensation of diphenylamine and sulphur, which on nitration yielded 1-nitrophenothiazine. Reduction of this compound afforded 1-aminophenothiazine dihydrochloride and subsequent protection of this product with acetic anhydride gave 1-acetylaminophenothiazine. The nitration of this acetylated compound yielded two isomeric compounds: 1-amino-2-nitrophenothiazine and 1-amino-4-nitrophenothiazine. The reduction of the ortho isomer furnished 1,2-diaminophenothiazine which when added to catecol and refluxed with ethanol gave the pentacyclic product 13H-5,14-dihydroquinoxalino[2,3-a]phenothiazine. Structures were established by analytical and spectral data. The results of the neuropharmacological screening data revealed that the novel system possessed neurosedative properties. The ability of this compound to antagonise fortwin – induced climbing behaviour in mice was correlated with neuroleptic potential. Key words: 13H-5,14-dihydroquinoxalino[2,3-a]phenothiazine, pentacyclic, phenothiazine, neurosedative, fortwin-induced.

ANTIPLASMODIAL TRITERPENOIDS ISOLATED FROM CANTHIUM MULTIFLORUM

In Burkina Faso, roots of Canthium multiflorum (Thonn.) Hiern (Rubiaceae) are used for the treatment of malaria and hypertension [1]. This investigation was initiated because of the absence of published phytochemical reports on this specie and the possibility of the presence of antiplasmodial compounds. A bioactivity guided fractionation of roots of Canthium multiflorum led to the isolation of the 2 new ursenoic acid derivatives, 19α-hydroxy-3-oxo-ursa-1,12-dien-28-oic acid 1 and 3-oxo-15α,19α-dihydroxyursa-1,12-dien-28-oic acid 2 which were tested for antiplasmodial effect and for inducing change of the shape of membranes of erythrocytes. Assay for antiplasmodial activity was performed using chloroquine-sensitive Plasmodium falciparum strain 3D7 [2]. Chloroquine was used as a positive control. Investigation of membrane shape effects of pentacyclic triterpenes was performed according to a previous described method (Ziegler et al., 2002) [3]. The structure of the two new compounds was elucidated using MS and NMR spectroscopy. The HR-ESI-MS gave a m/z 467.3161, calcd. for C30H43O4 (M-H)- 467.3167 for 1 and m/z = 507.3089 [M+ Na]+ (calcd. for C30H44NaO5 :507.3081) for compound 2. Application of the modified octant rule and comparison of the recorded CD spectrum with those of related pentacyclic triterpenoids with a 1-en-3-one system in the A-ring confirmed the absolute configuration of the two compounds. A moderate antiplasmodial activity (IC50=26 μg/ml) was observed which was not related to the deformation of the shape of erythrocyte membranes.

PENTACYCLIC TRITERPENES INTERVENTIONS IN SKIN PATHOLOGY/TOXICITY AND TREATMENT: IN VITRO AND IN VIVO CORRELATIONS

To identify a candidate compound for therapy of skin photoaging and skin carcinoma we used pentacyclic triterpenes, lupan type. Betulinic acid at lower concentration shown an important antitumor activity on K562 (human caucasian chronic myelogenous leukaemia), A2058 (human malignant lymph node melanoma) aspect dependent on active compound concentration and biologic medium (Dehelean C. et al 2008). Related compounds such as betulin and lupeol determined similar activity/toxicity with differences link to cell type and are active with low toxicity on A431 (human epithelial carcinoma) cell line. This is one of the results of our work present in this study. The compounds were dissolved by modern techniques: cyclodextrin mixing, PVP co-precipitation, etc. In vitro data were correlated with in vivo on animal and embryonated egg model. For in vivo analysis we applied FT-Raman measurements and initial results shown differences of skin dependent on applied compound. Anyway pentacyclic triterpenes are important antitumor compounds with a low toxicity

Leaf Production Plant

PLANT BIOLOGY Leaf epidermis, usually a single layer of cells, negotiates the balance between environmental factors and internal physiology. Leaf epidermal cells synthesize a wax that serves as a protective surface barrier and also synthesize a variety of complex metabolites important in plant defense. Leaves of the Madagascar periwinkle ( Catharanthus roseus ), long known as an herbal medicine, synthesize the alkaloids vinblastine and vincristine, which have valuable anticancer activities. In the search for other useful alkaloids or metabolites, Murata et al. have exploited RNA analysis of the leaf epidermis. C. roseus epidermis is rich in a variety of biosynthetic pathways, including those for flavonoids, lipids, and pentacyclic triterpenes. Analysis of RNAs expressed in leaf epidermis revealed much more complexity of the biochemistry occurring in leaves than did similar analytic approaches using broader tissue samples of the plant. The diversity of biosynthetic pathways represented in the leaf epidermis, combined with the variable destinations of the products, makes this single layer of cells look like the busiest of production and distribution centers. PJH Plant Cell 10.1105/tpc.107.056630 (2008).

Psidium guajava L: A review

Psidium guajava L, belonging to the Myrtacea family, has been reported to have anti-diarrheal, hepatoprotective, hypoglycemic, lipid lowering, antibacterial and antioxidant activities. It contains important phytoconstituents such as tannins, triterpenes, fl avonoid: quercetin, pentacyclic triterpenoid:guajanoic acid, saponins, carotenoids, lectins, leucocyanidin, ellagic acid, amritoside, beta-sitosterol,uvaol, oleanolic acid and ursolic acid. In view of the immense medicinal importance of the plant, this review is an eff ort to compile all the information reported on its phytochemical and pharmacological activities. Th e present review is an attempt to generate interest among the masses regarding its immense potential in preventing and treating several common diseases. Key words: Psidium guajava L, Myrtaceae, quercetin, guajanoic acid

Tonantzitlolone and other Diterpenes from Stillingia sanguinolenta

AbstractCembrene A (1), two novel diterpenes 2 and 3 with the rare flexibilane skeleton, two new pimaranes 4 and 5, sevenkauranes 6–12 (9 and 12 new), three known atisanes 13–15, a new trachylobane 16, and the new pentacyclic diterpene sanguinolane 17 with a novel skeleton were obtained from Stillingia sanguinolenta. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

A First Approach to the cis‐trans‐cis‐Photocyclodimers of 1,2‐Naphthoquinone

AbstractOn irradiation (λ=350 nm), 1,2‐naphthoquinone (=naphthalene‐1,2‐dione) monoacetals 1 are converted quantitatively to mixtures of the cis‐trans‐cis‐photocyclodimers 2 and 3. Careful hydrolysis of each of the (parent) pentacyclic diacetals 2a and 3a affords the – rather unstable – compounds 4 and 5, respectively.

Formation of a Bowl‐Shaped, Pentacyclic Phosphonium Cage by Methylation of a Nucleophilic Phosphinidene

Dominocyclisierung zweier Phosphinidenmoleküle: Die Methylierung des nucleophilen Phosphinidens 1 mit Methyltriflat liefert den ungewöhnlichen Phosphoniumkäfig 2, was für das Phospheniumion 3 als reaktive Zwischenstufe spricht.

Cycloadditions of isobenzofuran to a constrained template bearing neighboring dienophiles.

A high yielding synthesis of the pentacyclic diene-dione 1 has enabled investigation of its reactivity as a double dienophile in Diels-Alder [4+2] cycloadditions with isobenzofuran, leading to novel and highly symmetrical three-sided cavitands 3 and 4.

ChemInform Abstract: Synthesis of Pentacyclic 7β,15β‐Ethano Steroids.

ChemInform Abstract: Synthesis of Pentacyclic 7β,15β‐Ethano Steroids.

Bruceantin support studies. 12. Synthesis of a pentacyclic ABCDE bruceantin intermediate

Bruceantin support studies. 12. Synthesis of a pentacyclic ABCDE bruceantin intermediate

Synthesis of benzo[4,5]phenaleno[1,9‐bc]thiophene and benzo[4,5]phenaleno[9,1–6c]thiophene

AbstractTwo pentacyclic thiophenes, benzo[4,5]phenaleno[1,9–6c]thiophene (1) and benzo[4,5]phenaleno[9,1‐bc]‐thiophene (2) were synthesized via the corresponding 3‐methylphenanthro[2,1‐b]thiophene (7) and 1‐methylanthra[2,1–6]thiphene (19).

Aplotaxene epoxide from Cirsium hypoleucum

Aplotaxene epoxide (11,12-epoxyheptadeca-1,8,14-triene) was isolated from the roots of Cirsium hypoleucum. The pentacyclic tritepenes lupeol, taraxasterol and β-amyrin, and other acetates, were identified in C. hypoleucum, C. canum and C. carolinianum.