Allanxanthone B, a polyisoprenylated xanthone from the stem bark of Allanblackia monticola Staner L.C

In addition to five known compounds including three xanthones, tovophyllin A, rubraxanthone and garciniafuran, one pentacyclic triterpene, lupeol and one phytosterol, stigmasterol, a polyisoprenylated xanthone named allanxanthone B was isolated from the stem bark of Allanblackia monticola. The structure of the new compound was assigned as 2-geranyl-1,3,6-trihydroxy-2',2'-dimethyl[5',6':7,8]xanthone by means of spectroscopic analysis. The antimicrobial activities of some of these compounds against a range of micro-organisms are also reported.     

Major xanthones from Garcinia quadrifaria and Garcinia staudtii stem barks

The stem bark of Garcinia quadrifaria has yielded the novel xanthone 1, 3, 5-trihydroxy-4, 8-di(3,3-dimethylallyl)xanthone and the biflavonoids O-methylfukugetin and morelloflavone. The seeds contained the biflavonoids but not the xanthone. G. staudtii stem bark gave rheediaxanthone-A and the polyisoprenylated benzophenone xanthochymol. .     

An overview on genus garcinia: phytochemical and therapeutical aspects

The genus Garcinia belongs to the family Clusiaceae and has been involved in ayurvedic preparations to medicate various pathophysiological disorders. The bioactive molecules like hydroxycitric acid (HCA), flavonoids, terpenes, polysaccharides, procyanidines and polyisoprenylated benzophenone derivatives like garcinol, xanthochymol and guttiferone isoforms have been isolated from the genus Garcinia. The genus has received the attention of pharmaceutical industries due to their immense remedial qualities. The HCA has been known for its hypolipidemic property. The polyisoprenylated benzophenone and xanthone derivatives are known for their antioxidant, apoptotic, anti-cancer, anti-inflammatory, anti-bacterial, anti-viral, anti-fungal, anti-ulcer, anti-protozoal, and HAT inhibiting properties. Future studies on the synthesis of therapeutically important products and their analogs and evaluation of their safety and efficacy would be of great interest. Though the genus includes more than 300 species, we have made an effort to conceive the curative qualities of bioactive compounds of selected plants to the best of our knowledge.     

Natural polyprenylated benzophenone: keto-enol tautomerism from density functional calculations and the AIM theory

The quantum theory of atoms in molecules (QTAIM) and density functional theory (DFT) calculations were employed to investigate the structure and tautomeric equilibrium of epiclusianone, a polyisoprenylated benzophenone with interesting biological activities. Two different exchange-correlation functionals were employed, namely ωB97x-D and M06-2x, including implicit solvent models (benzene and DMSO). Our results for the thermodynamic properties show that the isomer in which the H atom is bonded to the oxygen away from the benzene ring is the most stable tautomer form of the epiclusianone, thus confirming previous charge density analysis from X-ray diffraction data (Martins et al. J Braz Chem Soc 18(8):1515–1523, 22).     

Xanthones and benzophenones from Garcinia griffithii and Garcinia mangostana

A new polyisoprenylated benzophenone, guttiferone I, together with the known compounds cambogin, 1,7-dihydroxyxanthone, 1,3,6,7-tetrahydroxyxanthone and 1,3,5,6-tetrahydroxyxanthone were isolated from the stem bark of Garcinia griffithii. The acetone extract of the heartwood of Garcinia mangostana contained one new diprenylated xanthone (mangoxanthone) and a new benzophenone (3',6-dihydroxy-2,4,4'-trimethoxybenzophenone) as well as the known xanthones dulxanthone D, 1,3,7-trihydroxy-2-methoxyxanthone, 1,3,5-trihydroxy-13,13-dimethyl-2H-pyran[7,6-b]xanthen-9-one. Their structures were established on the basis of spectroscopic studies and chemical correlation.     

Chemical and Biological Aspects of Garcinol and Isogarcinol: Recent Developments

The natural polyisoprenylated benzophenone derivatives garcinol and isogarcinol are secondary plant metabolites isolated from various Garcinia species including Garcinia indica. This review takes stock of the recent chemical and biological research into these interesting natural compounds over the last five years. New biological sources and chemical syntheses are discussed followed by new insights into the activity of garcinol and isogarcinol against cancer, pathogenic bacteria, parasite infections and various inflammatory diseases.     

Polyisoprenylated benzophenones from Clusia floral resins

From the floral resins of various Clusia species, seven polyisoprenylated benzophenones were isolated. HPLC allowed their quantification in all resins, revealing a distribution of benzophenone derivatives distinct from each other. In some species the staminal oils were collected and oleic, stearic and palmitic acids were the main constituents.     

Proteins are polyisoprenylated in Arabidopsis thaliana

Isoprenoid lipids were found to be covalently linked to proteins of Arabidopsis thaliana. Their identity (polyprenols: Prenol-9-11 with Pren-10 dominating and dolichols: Dol-15-17 with Dol-16 dominating) was confirmed by means of HPLC/ESI-MS with application of the multiple reaction monitoring technique as well as metabolic labeling of Arabidopsis plants with [³H]mevalonate and other precursors. The occurrence of typical farnesol-, geranylgeraniol-, and phytol-modified proteins was also noted. Radioisotopic labeling allowed detection of several proteins that were covalently bound to mevalonate-derived isoprenoid alcohols. A significant portion of polyisoprenylated proteins was recovered in the cytosolic/light vesicular fraction of Arabidopsis cells upon subfractionation. Taken together our data prove that a subset of plant proteins is polyisoprenylated.     

Enantioselective inhibitory abilities of enantiomers of notoamides against RANKL-induced formation of multinuclear osteoclasts

The marine-derived Aspergillus protuberus MF297-2 and the terrestrial A. amoenus NRRL 35600 produce enantiomeric prenylated indole alkaloids. Investigation of biological activities of the natural and synthetic derivatives revealed that (?)-enantiomers of notoamides A and B, 6-epi-notoamide T, and stephacidin A inhibited receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)–induced osteoclastogenic differentiation of murine RAW264 cells more strongly than their respective (+)-enantiomers. Among them, (?)-6-epi-notoamide T was the most potent inhibitor with an IC₅₀ value of 1.7 μM.     

Has the Bacterial Biphenyl Catabolic Pathway Evolved Primarily To Degrade Biphenyl? The Diphenylmethane Case

In this work, we have compared the ability of Pandoraea pnomenusa B356 and of Burkholderia xenovorans LB400 to metabolize diphenylmethane and benzophenone, two biphenyl analogs in which the phenyl rings are bonded to a single carbon. Both chemicals are of environmental concern. P. pnomenusa B356 grew well on diphenylmethane. On the basis of growth kinetics analyses, diphenylmethane and biphenyl were shown to induce the same catabolic pathway. The profile of metabolites produced during growth of strain B356 on diphenylmethane was the same as the one produced by isolated enzymes of the biphenyl catabolic pathway acting individually or in coupled reactions. The biphenyl dioxygenase oxidizes diphenylmethane to 3-benzylcyclohexa-3,5-diene-1,2-diol very efficiently, and ultimately this metabolite is transformed to phenylacetic acid, which is further metabolized by a lower pathway. Strain B356 was also able to cometabolize benzophenone through its biphenyl pathway, although in this case, this substrate was unable to induce the biphenyl catabolic pathway and the degradation was incomplete, with accumulation of 2-hydroxy-6,7-dioxo-7-phenylheptanoic acid. Unlike strain B356, B. xenovorans LB400 did not grow on diphenylmethane. Its biphenyl pathway enzymes metabolized diphenylmethane, but they poorly metabolize benzophenone. The fact that the biphenyl catabolic pathway of strain B356 metabolized diphenylmethane and benzophenone more efficiently than that of strain LB400 brings us to postulate that in strain B356, this pathway evolved divergently to serve other functions not related to biphenyl degradation.     

Isolation,characterization and cytotoxic activity of benzophenone glucopyranosides from Mahkota Dewa (Phaleria macrocarpa (Scheff.) Boerl)

Two benzophenone glucopyranosides have been isolated from the nut shell part of Mahkota Dewa. The structures were identified as 2,4′,6-trihydroxy-4-methoxy-benzophenone-2-O-β-d-glucoside (Mahkoside A) and 2,4′,6-trihydroxy-4-methoxy-6″-acetyl-benzophenone-2-O-β-d-glucoside (Mahkoside B). Mahkoside B was recognized as a novel compound. Furthermore, a series of benzophenone glucopyranoside derivatives (compounds 3–18) were synthesized and their bioactivities were characterized. Our results demonstrated that compound 18 has significant cytotoxicity against two esophageal cancer cell lines, stomach cancer cell line and prostate cancer cell line, with IC₅₀ less than 10 μM, indicating its potential activity against cancer cells.     

Two polyisoprenylated benzophenones from the trunk latex of Clusia grandiflora (Clusiaceae)

The polyisoprenylated benzophenones, chamones I and II, were isolated from the trunk latex of Clusia grandiflora (Clusiaceae) growing in southeastern Venezuela. A third benzophenone, nemorosone II, was isolated from the pollinator reward resin of the female flowers of the same plant. Chamone I and nemorosone II are structurally similar, differing only in the degree of prenylation. Bioassays of chamone I and nemorosone II using the honeybee pathogens, Paenibacillus larvae and Paenibacillus alvei, demonstrate that both have potent antibacterial activity, and that their structural differences affect both their bactericidal efficacies and their aqueous mobilities.     

Effects of nemorosone,isolated from the plant Clusia rosea,on the cell cycle and gene expression in MCF-7 BUS breast cancer cell lines

Background: Breast cancer is the cause of considerable morbidity and mortality in women. While estrogen receptor antagonists have been widely used in breast cancer treatment, patients have increasingly shown resistance to these agents and the identification of novel targeted therapies is therefore required. Nemorosone is the major constituent of the floral resin from Clusia rosea and belongs to the class of polycyclic polyisoprenylated benzophenones of the acylphloroglucinol group. The cytotoxicity of nemorosone in human cancer cell lines has been reported in recent years and has been related to estrogen receptors in breast cancer cells.Methods: Changes induced by nemorosone in the cell cycle and gene expression of the MCF-7 BUS (estrogen-dependent) breast cancer cell line were analyzed using flow cytometry and the RT² Profiler PCR array, respectively.Results: In comparison to breast cancer cells without treatment, nemorosone induced discrete cell cycle arrest in the G1 phase and significant depletion in the G2 phase. Moreover, the compound altered the expression of 19 genes related to different pathways, especially the cell cycle, apoptosis and hormone receptors.Conclusion: These promising results justify further studies to clarify mechanisms of action of nemorosone, in view of evaluate the possible use of this benzophenone as adjuvant in the treatment of breast cancer.     

(−)-trans-7(S)-Methoxytetradec-4-enoic acid and related amides from the marine cyanophyte Lyngbya majuscula

(?)-trans-7(S)-Methoxytetradec-4-enoic acid and the related amides, malyngamides A, B and C, were found as constituents of shallow-water varieties of the marine blue-green alga Lyngbya majuscule.     

Polyisoprenylated benzophenones from Garcinia semseii (Clusiaceae)

Three novel polyisoprenylated benzophenones, semsinones A–C have been isolated from the stem bark of Garcinia semseii together with a known monocyclic triterpene, achilleol A. The structures of the new compounds have been determined by analysis of the spectroscopic data and comparison of the NMR data with those of the closely related compounds previously reported.     

Effect of the ratio of (+) and (−) mating type of Blakeslea trispora on carotene production from cheese whey in submerged fermentation

The effect of the ratio of (+) and (?) mating type of Blakeslea trispora on carotene production from deproteinized hydrolysed whey in shake flask culture was investigated. Also, the inoculum ratio of the two mating types on the morphology of the microorganism and the relationship between morphological changes of the fungus and product formation were studied. The concentration of carotenes was significantly affected by the ratio of (+) and (?) mating type of B. trispora. A ratio of 1:10 up to 1:100 of (+) and (?) type was found to achieve the highest carotene yields. The optimum ratio of the (+) and (?) mating types for the maximum pigment production (175.0 mg/g dry biomass at 8 days of fermentation) was found to be 1:10. The carotene content in B. trispora consisted of β-carotene, γ-carotene, and lycopene. At the maximum concentration of carotenes the proportion of β-carotene, γ-carotene, and lycopene (as percent of total carotenes) was 80, 12, and 8%, respectively. B.trispora growing in submerged fermentation is able to develop complex morphologies which have been classified into three major groups: freely dispersed hyphae, clumps and pellets. These parameters are strongly influence the production of carotenes.     

Garcinol suppresses RANKL-induced osteoclastogenesis and its underlying mechanism

Osteoclasts (OCs) are multinuclear giant cells responsible for bone resorption, and an excessive bone resorption by OCs plays an important role in osteoporosis. Commonly used drugs for the treatment of osteoporosis have severe side effects. As such, identification of alternative treatments is essential. Garcinol, a polyisoprenylated benzophenone extracted from the fruit of Garcinia indica, has shown a strong antitumor effect through the nuclear factor-κB (NF-κB) and mitogen-associated protein kinases (MAPK) signaling pathways. However, the role of garcinol in the osteoclastogenesis is still unclear. Here, we demonstrated that garcinol can inhibit the receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis, osteoclastogenesis-related gene expression, the f-actin ring, and resorption pit formation. In addition, garcinol abrogated RANKL-induced osteoclastogenesis by attenuating the degradation of the MAPK, NF-κB, and PI3K-AKT signaling pathway as well as downstream factors c-jun, c-fos, and NFATC1. In vivo, suppression of osteoclastogenesis by garcinol was evidenced by marked inhibition of lipopolysaccharide-induced bone resorption. In conclusion, our data demonstrated that garcinol inhibited the RANKL-induced osteoclastogenesis by suppressing the MAPK, NF-κB, and PI3K-AKT signaling pathways and thus has potential as a novel therapeutic option for osteolytic bone diseases.     

Slit Injection of 1,3-Dichloropropene for Management of Belonolaimus longicaudatus on Established Bermudagrass

Belonolaimus longicaudatus is a serious problem on bermudagrass, a common warm-season turfgrass, in Florida. The cancellation of organophosphate nematicides necessitates that new management tools be identified for use on sports turf. Postplant application of 1,3-dichloropropene (1,3-D) on bermudagrass was evaluated for management of B. longicaudatus on golf course fairways and driving ranges. A series of 10 experiments were conducted to evaluate the effectiveness of 1,3-D in reducing population densities of B. longicaudatus and enhancing bermudagrass recovery from nematode damage. In 5 of 10 experiments, 1,3-D injected at 46.8 liters/ha was effective in reducing population densities of B. longicaudatus (P < 0.05) compared to untreated plots 2 to 4 weeks after treatment. One month after treatment, population densities of B. longicaudatus ranged from 59% to 97% of those in untreated plots. Nematode suppression generally lasted 2 months or less. Turf visual performance was improved following injection with 1,3-D (P < 0.05) over untreated plots when other factors were not limiting. Turf root development also was enhanced following injection with 1,3-D. Postplant injection of 1,3-D could be a useful nematode management tool for certain sports turf applications.     

Total syntheses and stereochemical reassignments of mollenines A and B

Total syntheses of prenylated pyrrolidinoindoline alkaloids, (?)-mollenines A [(?)-1′] and B (2′), were accomplished via three- and four-step sequences including a bioinspired indole prenylation reaction followed by dioxomorpholine ring formation. Then, the stereochemistry of mollenines A and B was reassigned to 3S,6S,14S,16S by analysis of spectroscopic data and chemical syntheses with different approaches along with the comparison of calculated and experimental ECD spectra. In addition, a thermodynamically controlled epimerization reaction on the dioxomorpholine ring was observed in our synthesis.     

Polyisoprenylated benzophenones in cuban propolis; biological activity of nemorosone

The Copey tree (Clusia rosea) has a large distribution in Cuba and its floral resin is a rich source of polyisoprenylated benzophenones. To determine the presence of these natural products, we carried out a study by HPLC of 21 propolis samples produced by honey bees (Apis mellifera) from different provinces of Cuba. Nemorosone resulted to be the most abundant polyisoprenylated benzophenone and the mixture of xanthochymol and guttiferone E was also observed, but in minor proportion. We studied the biological activity of the pure natural product nemorosone and its methyl derivatives. We found that nemorosone has cytotoxic activity against epitheloid carcinoma (HeLa), epidermoid carcinoma (Hep-2), prostate cancer (PC-3) and central nervous system cancer (U251). It also exhibited antioxidant capacity. Methylated nemorosone exhibited less biological activity than the natural product.