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Two new nor-ent-halimane diterpenes and three previously unreported nor -clerodane diterpenes, designated callicaintides A−E (1−5), were isolated from Callicarpa integerrima. Compounds 1 and 2 feature a distinctive 5/6-membered ring system, while compounds 3−5 are characterized by progressively truncated carbon skeletons, containing 18, 17, and 16 carbons, respectively. In addition, four known compounds 6−9 were also identified. Their structures were elucidated using advanced spectroscopic techniques, including nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), ultraviolet (UV), infrared radiation (IR), optical rotatory dispersion (ORD), DP4+ analysis and electronic circular dichroism (ECD), supported by quantum chemical calculations. Compounds 1−9 were evaluated for their anti-MRSA activity. Among them, compound 6 demonstrated significant anti-MRSA activity, with a minimum inhibitory concentration (MIC) of 16 μg·mL−1. [ABSTRACT FROM AUTHOR]

Safer analgesic drugs remain a hard challenge because of cardiovascular and/or gastrointestinal toxicity, mainly. So, this study evaluated in vivo the antiproliferative actions of a fraction with casearins (FC) from Casearia sylvestris leaves against human colorectal carcinomas and antihyperalgesic effects on inflammatory- or opiate-based pain relief and oncologic pain in Sarcoma 180 (S180)-bearing mice. Moreover, docking investigations evaluated the binding among Casearin X and NMDA(N-methyl-D-aspartate)-type glutamate receptors. HCT-116 colorectal carcinoma-xenografted mice were treated with FC for 15 days. Antinociceptive assays included chemically induced algesia and investigated mechanisms by pharmacological blockade. Intraplantar region S180-bearing animals received a single dose of FC and were examined for mechanical allodynia and behavior alterations. AutoDock Vina determined molecular interactions among Cas X and NMDA receptor subunits. FC reduced tumor growth at i.p. (5 and 10 mg/kg) and oral (25 mg/kg/day) doses (31.12–39.27%). FC reduced abdominal pain, as confirmed by formalin and glutamate protocols, whose antinociception activity was blocked by naloxone and L-NAME (neurogenic phase) and naloxone, atropine, and flumazenil (inflammatory phase). Meanwhile, glibenclamide potentiated the FC analgesic effects. FC increased the paw withdrawal threshold without producing changes in exploratory parameters or motor coordination. Cas X generated a more stable complex with active sites of the NMDA receptor GluN2B subunits. FC is a promising antitumor agent against colorectal carcinomas, has peripheral analgesic effects by desensitizing secondary afferent neurons, and inhibits glutamate release from presynaptic neurons and/or their action on cognate receptors. These findings emphasize the use of clerodane diterpenes against cancer-related pain conditions. [ABSTRACT FROM AUTHOR]

New substances with antimicrobial properties are needed to successfully treat emerging human, animal, or plant pathogens. Seven clerodane diterpenes, previously isolated from giant goldenrod (Solidago gigantea) root, were tested against Gram-positive Bacillus subtilis, Bacillus spizizenii and Rhodococcus fascians by measuring minimal bactericidal concentration (MBC), minimal inhibitory concentration (MIC) and half-maximal inhibitory concentration (IC50). Two of them, Sg3a (a dialdehyde) and Sg6 (solidagoic acid B), were proved to be the most effective and were selected for further study. Bacillus spizizenii was incubated with the two diterpenes for shorter (1 h) or longer (5 h) periods and then subjected to genome-wide transcriptional analyses. Only a limited number of common genes (28 genes) were differentially regulated after each treatment, and these were mainly related to the restoration of cell membrane integrity and to membrane-related transports. Changes in gene activity indicated that, among other things, K+ and Na+ homeostasis, pH and membrane electron transport processes may have been affected. Activated export systems can be involved in the removal of harmful molecules from the bacterial cells. Inhibition of bacterial chemotaxis and flagellar assembly, as well as activation of genes for the biosynthesis of secondary metabolites, were observed as a general response. Depending on the diterpenes and the duration of the treatments, down-regulation of the protein synthesis-related, oxidative phosphorylation, signal transduction and transcription factor genes was found. In other cases, up-regulation of the genes of oxidation–reduction processes, sporulation and cell wall modification could be detected. Comparison of the effect of diterpenes with the changes induced by different environmental and nutritional conditions revealed several overlapping processes with stress responses. For example, the Sg6 treatment seems to have caused a starvation-like condition. In summary, there were both common and diterpene-specific changes in the transcriptome, and these changes were also dependent on the length of treatments. The results also indicated that Sg6 exerted its effect more slowly than Sg3a, but ultimately its effect was greater. [ABSTRACT FROM AUTHOR]

The phytochemical profile of essential oils and extracts from Casearia sylvestris leaves, flowers and fruits have been investigated here. Leaf and flower extracts were prepared by sonication and analyzed by thin-layer chromatography and high-performance liquid chromatography. The phenolic content was determined by ultraviolet spectrophotometry. Leaves, flowers, and fruits essential oils were extracted by hydrodistillation. The highest extracts yields were 20.3 % (leaves) and 23.4 % (flowers) with ethanol 70 %. Essential oil extraction yields were 0.3 % (leaves) and 0.1 % (flowers and fruits). Bicyclogermacrene was the major component in all essential oil. Thin-layer chromatography suggests a chemical profile similar for leaves and flowers. The leaves and flowers phenolic content were similar (14.0 and 15.0 %, respectively). Chromatography analyses indicated the predominance of casearin clerodane diterpenes in leaves (λmax 232-235), whereas in flowers, diterpenes with a different standard diene in side-chain C13(16) and C14 (λmax 223-229). The different phytochemical profile of C. sylvestris flowers as compared to the leaves could be explored by the search for new bioactive components. This is the first report on the fruit and flower C. sylvestris essential oil composition. These data could be used as quality control of herbal medicine derived from C. sylvestris leaves.

Nowadays, new leishmanicidal drugs are needed and natural products arise as a promising alternative source. Therefore, bioguided fractionation of a hydroethanolic extract from the stem bark of Croton echioides Baill. were conducted based on its antileishmanial activity. Two novel neo-clerodane diterpenoids methyl-15,16-epoxy-3,13(16),14-neo-clerodatrien-17,18-dicarboxylate (1) and dimethyl-3-oxo-15,16-epoxy-13(16),14-neo-clerodadien-17,18-dicarboxylate (2) were isolated, as well as four known compounds (3–6) and lupeol, from the hexane fraction. Their structures were established by NMR analysis. The crude extract, fractions and the compounds (1 and 3–6) were evaluated for their in vitro antileishmanial activity and cytotoxicity against macrophages J774A.1. The selectivity index (SI) were calculated. The most active compound against promastigote forms of L. amazonensis was the clerodane diterpene 4, with IC50 values of 8.3 µM and SI value of 80.9. Our results highlighted stem bark of Croton echioides Baill. as a promising source for the development of a new chemotherapeutic agent to combat leishmaniasis. [ABSTRACT FROM AUTHOR]

Six previously undescribed clerodane diterpenes, cardorubellas A-F (1 - 6), along with seven known ones (7 - 13), were isolated from the aerial parts of Callicarpa pseudorubella. Their chemical structures were established by analysis of 1D and 2D NMR, HR-ESI-MS, X-ray diffraction, and electronic circular dichroism (ECD) data. Notably, cardorubella B (2) represented the first examples of naturally occurring succinic anhydride-containing clerodane diterpenes derivatives. The anti-proliferative activities of these compounds were assessed. Remarkably, compound 2 exhibited comparable inhibitory activity against HEL cell lines, surpassing the positive control with an IC 50 value of 14.01 ± 0.77 μM, compared to 17.02 ± 4.70 μM for 5-fluorouracil. [Display omitted] [ABSTRACT FROM AUTHOR]

More than 20 natural products have been reported to modulate PCSK9-mediated cholesterol regulation, and small-molecule-derived proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors continue to be developed and identified. Here, twelve undescribed clerodane-type diterpenes (1 – 9 and 12 – 14) and two known compounds were isolated from the chloroform-soluble extract of the dried fruits of Casearia grewiifolia Vent. using a PCSK9 mRNA expression monitoring assay. Among the undescribed compounds, the stereochemistry of two diastereomeric grewiifolins A and B (1 and 2) were extensively elucidated using 2D Nuclear Overhauser Effect Spectroscopy (NOESY) experiments, excitation-sculptured indirect detection experiments (EXSIDE), interproton distance analyses, and computational calculations that included quantum chemical shift calculations combined with DP4+ analysis. All isolates were assessed for their inhibitory activity against PCSK9 and IDOL mRNA expression. Among the compounds tested, compound 3 inhibited PCSK9 and IDOL mRNA expression. [Display omitted] • Twelve undescribed diterpenes were isolated from Casearia grewiifolia. • The stereochemistry of 1 and 2 was assigned by DP4+ and interproton distance analyses. • The isolates were investigated for their PCSK9 inhibitory effects. [ABSTRACT FROM AUTHOR]

Abstract As a part of our ongoing research program on compounds from higher plants with lactate dehydrogenase (LDH) and monoacylglycerol lipase (MAGL) inhibitory activities, three new neoclerodane diterpene 12-deacetylsplendidin C (1), pseudorosmaricin (2), and 2-dehydroxysalvileucanthsin A (3) along with six known compounds were isolated from Salvia pseudorosmarinus aerial part extracts. Their structures were determined by spectroscopic and spectrometric techniques including 1D- and 2D NMR, and MS analyses. The isolated diterpenes were assayed for their inhibitory activity on LDH5 and MAGL, two enzymes covering key roles in the peculiar energetic metabolism of malignant tumours. All the assayed diterpenes showed negligible activity on LDH5, whereas the known jewenol A (4) displayed a moderate inhibition activity on MAGL, showing an IC 50 value of 46.8μM and it proved to be a reversible MAGL inhibitor. Docking and molecular dynamic simulation studies where thus performed to evaluate the binding mode of 4 within MAGL. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

The phytochemical profile of essential oils and extracts from Casearia sylvestris leaves, flowers and fruits have been investigated here. Leaf and flower extracts were prepared by sonication and analyzed by thin-layer chromatography and high-performance liquid chromatography. The phenolic content was determined by ultraviolet spectrophotometry. Leaves, flowers, and fruits essential oils were extracted by hydrodistillation. The highest extracts yields were 20.3% (leaves) and 23.4% (flowers) with ethanol 70%. Essential oil extraction yields were 0.3% (leaves) and 0.1% (flowers and fruits). Bicyclogermacrene was the major component in all essential oil. Thin-layer chromatography suggests a chemical profile similar for leaves and flowers. The leaves and flowers phenolic contents were similar (14.0 and 15.0%, respectively). Chromatographic analyses indicated the predominance of casearin clerodane diterpenes in leaves (λmax 232-235), whereas in flowers diterpenes with a different standard diene in side-chain C13(16) and C14 (λmax 223-229). The different phytochemical profile of C. sylvestris flowers as compared to the leaves could be explored by the search for new bioactive components. This is the first report on the fruit and flower C. sylvestris essential oil composition. These data could be used as quality control of herbal medicine derived from C. sylvestris leaves. [ABSTRACT FROM AUTHOR]

Three new clerodane diterpenes, (4→2)-abeo-cleroda-2,13E-dien-2,14-dioic acid (1), (4→2)-abeo-2,13-diformyl-cleroda-2,13E-dien-14-oic acid (2), and 16(R&S)- methoxycleroda-4(18),13-dien-15,16-olide (3), were isolated from the unripe fruit of Polyalthia longifolia var. pendula (Annonaceae) together with five known compounds (4–8). The structures of all isolates were determined by spectroscopic analysis. The anti-inflammatory activity of the isolates was evaluated by testing their inhibitory effect on NO production in LPS-stimulated RAW 264.7 macrophages. Among the isolated compounds, 16-hydroxycleroda-3,13-dien-15,16-olide (6) and 16-oxocleroda-3,13-dien-15-oic acid (7) showed promising NO inhibitory activity at 10 µg/mL, with 81.1% and 86.3%, inhibition, respectively.

NMR and single crystal X-ray diffraction analysis of seven clerodanes from Mexican Salvia species was performed. We focused on clerodanes with tertiary hydroxyl group at C-4, C-8, and C-10, in which the establishment of absolute configuration around these chiral centers is nontrivial and the 13 C NMR signals can be misassigned. In addition, the analysis by 1 H NMR in aprotic solvent allowed us to establish a common pattern that correlates the chemical shift with the position of the hydroxyl groups, which constitute a good methodology for future structural elucidation of these kinds of compounds. The obtained data allowed us to establish the absolute configuration of five of these diterpenes and the structural revision of salvimicrophyllin D ( 7 ). [ABSTRACT FROM AUTHOR]

In recent years, clerodane diterpenes, a class of bioactive compounds, have come into the spotlight due to their amazing bioactivities. Three novel clerodane diterpene analogues were obtained by synthesising 16-hydroxycleroda-3,13(14)-Z-diene-15,16-olide (Lactone) with primary amines. Anti-tubercular activity was determined using Microplate Alamar Blue Assay. Among all the synthesised compounds from methanolic extract of seeds, results clearly showed that compounds 3 and 5 have significant anti TB activity with an MIC of 1.56 µg/ml against the Mycobacterium tuberculosis MTB H37Rv bacilli strain than the gold standard drugs pyrazinamide (3.13 µg/ml), ciprofloxacin (3.13 µg/ml), streptomycin (6.25 µg/ml) and rifampicin (6.25 µg/ml). Compound 5 exhibited significant antibacterial activity with zone of inhibition of 10.8 mm with Gram + ve and 7.95 mm with Gram -ve bacteria at a conc of 50 µg/ml respectively. In the current investigation, three novel heterocycles (compounds 3-5) of the diterpenoid were prepared, in high yield, using one-pot, efficient approach.

The marine sponge Raspailia bouryesnaultae, collected in South Brazil, was selected for detailed investigation considering the results of a screening that pointed to an in vitro antiproliferative effect against non-small cells of human lung cancer (A549) and anti-herpes activity against Herpes Simplex virus type 1 (KOS and 29R strains) of ethanolic extracts. The fractionation and chemical investigation of the sponge’s hexanic fraction led to the isolation and structural elucidation of six clerodane diterpenes. The main component was identified as the already-reported raspailol (1), isolated from a sponge of the same genus collected in New Zealand. The structure of a new diterpene (2) with a rearranged skeleton was established by high-resolution mass spectrometry (HRMS) and 1D and 2D Nuclear magnetic resonance spectroscopy (NMR) experiments, and named here as raspadiene. Furthermore, four diterpenes were elucidated as isomers of clerodane diterpenes previously obtained from plants, namely kerlinic acid (3), kerlinic acid methyl ester (4), annonene (5), and 6-hydroxyannonene (6). They differ in their stereochemistry, since these diterpenes are characterized by a trans ring fusion at the decalin moiety and the relative configuration of the two methyl groups at C-8 and C-9 in a cis relationship (type trans/cis). The Raspailia diterpenes have a cis ring fusion at the decalin moiety, and the two methyl groups at C-8 and C-9 are in a trans relationship (type cis/trans). The isolated compounds were evaluated for their potential antiproliferative effects on human cancer cell line A549, and it was observed that the diterpenes bearing a hydroxyl group at C-6 exhibited moderate cytotoxic activity, with 50% inhibitory concentration (IC50) values lower than 25 μM. The evaluation of the potential anti-herpes activity against Herpes Simplex Virus type 1 (HSV-1, KOS and 29R strains) showed that the more promising results were observed for the new compound 2, since it inhibited HSV-1 (KOS and 29R strains) replication by 83% and 74%, respectively.

Ethanolic extracts of the leaves of Casearia sylvestris yielded a novel clerodane diterpene, 15-hydroxy-3-cleroden-2-one, together with the known diterpenes (-)-hardwickiic acid, reported for the first time from this species, and casearins B and G, previously isolated from C. sylvestris. The structures of all four compounds were determined by spectrometric analysis. The new clerodane diterpene and (-)-hardwickiic acid contain structural features that are completely different from the highly oxygenated casearins and casearvestrins isolated from C. sylvestris.

Three new diterpenes (amarissinins A-C, 1-3) containing several oxygenated functionalities were isolated from the leaves and flowers of Salvia amarissima. The structures of these compounds were established through the analysis of their NMR spectroscopy and mass spectrometry data. The structures of compounds 1 and 2 were confirmed by single crystal X-ray diffraction. Compound 2 was identified as a C-10 epimer of dugesin F (5). The cytotoxic activity of these compounds against five human cancer cell lines was determined. Additionally, the capability to modulate the multidrug resistance (MDR) in the MCF-7 cancer cell line resistant to vinblastine was tested. [ABSTRACT FROM AUTHOR]

Two new clerodane-type diterpenes, tinosporins C (1) and tinosporins D (2) were isolated from the stems of Tinospora sagittata (Oliv.), together with three known ones, columbin (3), tinophylloloside (4), and tinospinoside D (5). The structures of these compounds were determined on the basis of spectroscopic data interpretation, with that of the absolute configuration of compound 1 was assigned by experimental and calculated ECD spectra. The cytotoxicity and α-glucosidase inhibitory activities of isolated compounds were evaluated in vitro. [ABSTRACT FROM AUTHOR]

Bio-activity directed investigation of hexane extract from the leaves ofPremna tomentosaled to the isolation of three new clerodane diterpenes (1–3) along with four known compounds (4–7). The structures of new compounds were established using IR, MS, 1D, and 2D NMR techniques. Thein vitrocytotoxicity of the crude hexane extract and the isolated compounds were evaluated against seven human cancer cell lines and results indicated that compounds2and4depicted significant cytotoxicity against hepatocellular carcinoma cell line. [ABSTRACT FROM AUTHOR]

Terpenoids from Salvia species have been identified to possess biological properties as antiprotozoal agents. Here, we evaluated the antiamoebic and antigiardial activities of 14 known clerodane and modified clerodane-type diterpenes isolated from five Mexican Salvia species against Entamoeba histolytica and Giardia lamblia, and analyzed the effects of the functionalities in decalin ring or in the whole clerodane framework to visualize the structural requirements necessary to produce an antiprotozoal activity. Among these, linearolactone was the most active clerodane diterpene against both protozoa with IC50 values of 22.9 μM for E. histolytica and of 28.2 μM in the case of G. lamblia. In this context it may be a lead compound for the development of novel therapeutic agent for the treatment of diarrhea and dysentery. The remaining diterpenes assayed showed moderate to weak activity against both protozoa. These findings give support to the use of Salvia species in the traditional medicine from México for the treatment of diarrhea. [ABSTRACT FROM AUTHOR]

From the aerial parts of Salvia adenophora Fernald four derivatives of 12-oxo-phytodienoic acid ( 1 – 4 ) together with five clerodane diterpenoids ( 5 , 6 , 8 – 10 ), and one known diterpene ( 7 ) have been isolated. Compounds 1 – 6 and 8 – 10 are described for the first time. The structures were established by extensive 1D, 2D NMR and HRESI-TOFMS spectroscopic methods. Finally, the absolute configuration has been established by comparing of experimental and quantum chemical calculation of ECD spectra. Despite a total lack of antimicrobial activity of the plant extract, hinting to the existence of antagonistic interactions in the crude material, three oxylipins ( 2 – 4 ) displayed a promising inhibition on Gram-positive multidrug-resistant clinical strains including Staphylococcus aureus , Streptococcus agalactiae and, particularly, Staphylococcus epidermidis , while the compounds 9 and 10 revealed a specific and strain-dependent activity against S. epidermidis . Interestingly, the inhibition provided by these compounds was independent of the resistance patterns of these pathogens to classic antibiotics. No action was reported on Gram-negative strains nor on Candida albicans . These results confirm that clerodanes and, particularly, prostaglandin-like compounds can be considered as interesting antimicrobial agents deserving further study. [ABSTRACT FROM AUTHOR]

In the West, the consumption of medicinal plants is increasing strongly, and up to 40% of the population use medicinal plants and phytotherapic preparations regularly, in the belief that they are innocuous and/or safe. However, in most cases there is no scientific proof of their pharmacological and toxicological properties. The aim of this study was to carry out a bibliographical review of the toxicological properties of Casearia sylvestris Swartz and collect data providing a basis for its rational use. Some studies validate classical therapeutic indications of C. sylvestris, such as to treat diarrhea and snakebites, justifying its empirical use. Nevertheless, there are few reports about its toxicological properties and these present only limited findings, describing results as 50% lethal dose (LD50) and the acute toxicity of its constituents. Currently, research is insufficient to ensure safety of popular preparations based on C. sylvestris. Therefore, it is necessary to make a fuller assessment of its deleterious profile, especially with respect to the toxic potential of its constituents, as well as its capacity to harm target organs and organic systems. [ABSTRACT FROM AUTHOR]

Abstract: Leishmaniasis and Chagas disease are infectious diseases caused by parasite Leishmania sp. and Trypanosoma cruzi, respectively, and are included among the most neglected diseases in several underdeveloped and developing countries, with an urgent demand for new drugs. Considering the antiparasitic potential of MeOH extract from leaves of Casearia sylvestris Sw. (Salicaceae), a bioguided fractionation was conducted and afforded four active clerodane diterpenes (casearins A, B, G, and J). The obtained results indicated a superior efficacy of tested casearins against trypomastigotes of T. cruzi, with IC50 values ranging from 0.53 to 2.77μg/ml. Leishmania infantum promastigotes were also susceptible to casearins, with IC50 values in a range between 4.45 and 9.48μg/ml. These substances were also evaluated for mammalian cytotoxicity against NCTC cells resulting in 50% cytotoxic concentrations (CC50) ranging from 1.46 to 13.76μg/ml. Additionally, the action of casearins on parasite membranes was investigated using the fluorescent probe SYTOX Green. The obtained results demonstrated a strong interaction of casearins A and B to the plasma membrane of T. cruzi parasites, corroborating their higher efficacy against these parasites. In contrast, the tested casearins induced no alteration in the permeability of plasma membrane of Leishmania parasites, suggesting that biochemical differences between Leishmania and T. cruzi plasma membrane might have contributed to the target effect of casearins on trypomastigotes. Thus, considering the importance of studying novel and selective drug candidates against protozoans, casearins A, B, G, and J could be used as tools to future drug design studies. [Copyright &y& Elsevier]

Phytochemical investigation of the methylenechloride/methanol extract of the aerial parts of Stachys aegyptiaca afforded a new neoclerodane-type diterpene with a new side chain 1, in addition to two known diterpenes 2 and 3 and a known flavonoid glycoside 4. The structures of the compounds were determined by comprehensive NMR studies including DEPT, COSY, NOESY, HMQC, HMBC and HR-MS. [ABSTRACT FROM AUTHOR]

Abstract: Our ongoing research to identify natural growth inhibitors with diterpene and triterpene skeletons exuding from the surface of the aerial parts of Salvia species led us to study Salvia miniata Fernald. Ten clerodane diterpenoids were found, along with three known diterpenes. Most of the isolated compounds from S. miniata inhibited the germination of Papaver rhoeas L. and Avena sativa L. in Petri dish experiments. Parallel results have been obtained in experiments carried out to evaluate the subsequent growth of the seedlings of the target species in the presence of the tested compounds. [ABSTRACT FROM AUTHOR]

Abstract: Clerodane diterpenes have demonstrated cytotoxic, antiplasmodial and anti-ulcer properties. In the present work, we determined the cytotoxic effect of casearin L (Cas L), O (Cas O) and X (Cas X) and (−)-hardwickiic acid isolated from Casearia sylvestris leaves, and investigated the underlying mechanisms involved in in vitro cell death induced by Cas X in HL-60 leukemia cells (0.7, 1.5 and 3.0μM). Cytotoxicity tests demonstrated that Cas X was the most active compound studied, showing greater cytotoxic effects against CEM and HL-60 lines (IC50 of 0.4μM) and human peripheral blood mononuclear cells (PBMC, IC50 of 1.2μM). After 24h exposure, Cas X caused a decrease in 5-bromo-20-deoxyuridine (BrdU) incorporation (36.6 and 24.5% labeling at 0.7 and 1.5μM, respectively), reduction in viability, and increase in apoptotic and necrotic leukemia cells in a dose-dependent manner evidenced by the trypan blue and AO/EB (acridine orange/ethidium bromide) assays. Moreover, Cas X-treated cells exhibited nuclear fragmentation and cytoplasmic vacuolization depending on the concentration tested. These characteristics of apoptosis or secondary necrosis were confirmed by flow cytometry which revealed DNA fragmentation, phosphatidylserine externalization, activation of the effector caspases 3/7 and mitochondrial depolarization. We then found evidence that Cas X causes cell death via apoptotic pathways, corroborating the potential of casearins as compounds with promising antitumor-related properties. [Copyright &y& Elsevier]

The ethanolic extract of Polyalthia longifolia var. pendula was fractionated to get a hexane-soluble residue, which led to the isolation of four clerodane diterpenes: (-)-3α,16α-dihydroxycleroda-4(18),13(14)Z-dien-15,16-olide (1), (-)-3β,16α-dihydroxycleroda-4(18), 13(14)Z-dien-15,16-olide (2), (-)-16α-hydroxycleroda-3,13(14)Z-dien-15,16-olide (3) and (-)-16-oxocleroda-3,13(14)E-dien-15-oic acid (4). Diterpene 1 is a new compound, while 2 is reported for first time from this plant. Both 1 and 2 were tested for their growth inhibitory activity on four cancer cell lines in vitro. IC50 values suggest that they are effective as cytotoxic agents. [ABSTRACT FROM AUTHOR]

Abstract: Three clerodane diterpenes were isolated and identified from leaf extract of Glossocarya calcicola. Compound 1 has been characterised as (rel)-10βH-trans-12ξ-(2-methylbut-2(E)-enoyl)-1β-(isobutanoyl)-6α,13ξ-dihydroxyclerodan-4(20),8(18)-dien-7,15-dione-15,16-oxide, to which we have assigned the trivial name calcicolin-A. The other two compounds had the same skeletal structure and C-12 substituent but in compound 2, the C-1 esterifying group becomes 2-methylbut-2(E)-enoic acid and in 3 it becomes 2-methylbutanoic acid. Although anti-insect activity was not observed for G. calcicola, cytotoxicity against insect and human carcinoma cell lines was detected. [Copyright &y& Elsevier]