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Two new styryl lactone derivatives, goniothapic acids A ( 1 ) and B ( 2 ), and 18 known compounds, were isolated from the twig and leaf extracts of Goniothalamus tapis Miq. The structures of new compounds were characterised by spectroscopic methods and HRESITOFMS. Their absolute configuration was established by comparing the experimental and calculated ECD spectra. Eleven compounds were evaluated for their α-glucosidase inhibitory activity. Of these, (-)-goniothalamin ( 5 ) and oldhamactam ( 16 ) showed the best α-glucosidase inhibitory activity with IC 50 values of 54.8 and 57.9 µM, respectively.

Graphical abstract Highlights • A new total synthesis of cardiobutanolide and two new analogues has been completed. • In vitro antitumour activity of this natural product and analogues was recorded. • (+)-Cardiobutanolide was identified as the most active compound. Abstract A new asymmetric synthesis of the naturally occurring styryl lactone cardiobutanolide and two novel analogues have been achieved starting from d -xylose. The key steps of the synthesis included an initial zinc mediated reductive THF-ring opening, stereoselective olefination and Sharpless asymmetric dihydroxylation. It was shown that cardiobutanolide (1) exhibits promising in vitro antitumour properties against certain human neoplastic cell lines. It was more potent than the commercial anticancer agent doxorubicin against three cell lines (K562, HL-60 and Raji). [ABSTRACT FROM AUTHOR]

Platelet-derived growth factor-BB (PDGF-BB) and its downstream effector, extracellular signal-regulated kinase 1/2 (ERK1/2) MAP kinase, initiate a multitude of biological effects, including vascular smooth muscle cell (VSMC) proliferation and migration, which are critical events in the initiation and development of restenosis following percutaneous transluminal coronary angioplasty (PTCA). Styryl lactones are natural products that have been demonstrated to possess anti-proliferative activities. Goniolactone C is a styryl lactone derivative that was first extracted from Goniothalamus cheliensis Hu. In the present study, we investigated the effects of goniolactone C on VSMC migration and proliferation. We found that goniolactone C preferentially interacted with cellular systems that rely on PDGF signaling but not those that rely on epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) signaling. Goniolactone C strongly inhibited PDGF-BB-induced VSMC migration and proliferation. goniolactone C-mediated inhibition of VSMC proliferation was associated with cell cycle arrest, while goniolactone C-mediated inhibition of VSMC migration was associated with the suppression of adhesion molecule expression. In addition, goniolactone C directly inhibited PDGFR-β kinase activity, thereby blocking the downstream effector of PDGF-BB. Thus, the results of the present study suggest a novel adjunctive pharmacological strategy that may be used to prevent angioplasty-related restenosis.

Diastereoselective first total synthesis of parvistone C 1 and C8-epimer 1a are described. The key features of our synthesis include Sharpless asymmetric dihydroxylation, stereoselective aryl Grignard reactions, Still–Gennari olefination, and intramolecular cyclization. [ABSTRACT FROM AUTHOR]

Racemic syn-ethyl ( E)-2-(2,2-dimethyl-6-styryl-1,3-dioxan-4-yl)acetate is hydrolyzed with high enantioselectivity by Novozyme-435 in 0.05 m sodium phosphate buffer at room temperature. The optically pure unreacted ethyl 2-((4 R,6 S)-2,2-dimethyl-6-(( E)-styryl)-1,3-dioxan-4-yl)acetate and hydrolyzed (4 S,6 R)-acid are used in the synthesis of HMG-CoA reductase inhibitor rosuvastatin and the naturally occurring styryl lactone cryptomoscatone E1, respectively. [ABSTRACT FROM AUTHOR]

This study is based on the analyses of the retention behavior of selected natural styryl lactones and their synthetic analogues in reversed-phase high-performance liquid chromatography. Chromatographic separations were achieved applying ZORBAX SB-C18 column and two different mobile phases: methanol-water and acetonitrile-water. Chromatographic lipophilicity of the analyzed compounds was defined by log k 0 constant and correlated with in silico molecular descriptors. According to the statistical validation parameters, obtained results indicate that the presented linear and multiple quantitative structure-retention relationship models can successfully predict the chromatographic lipophilicity of structurally similar compounds. Hierarchical cluster analyses (HCA) was applied in order to group similar compounds according to their chromatographic and in silico lipophilicity. It can be concluded that chromatographic systems with methanol-water were better for modelling of log k 0 . Modelling was performed in order to characterize compounds regarding their lipophilicity profiles as future drug candidates. [ABSTRACT FROM AUTHOR]

A series of new antitumour lactones containing the [3.3.0] bicyclic furano-lactone core and the halogen or azido group at the C-7 position have been designed, synthesized, and evaluated for their in vitro antitumour activity against a panel of human tumour cell lines. Some of the analogues displayed powerful antiproliferative effects to certain human tumour cells, but all of them were devoid of any cytotoxicity towards the normal foetal lung fibroblasts (MRC-5). A SAR study reveals the structural features of these lactones that may affect their antiproliferative activity. These are: the nature of substituent present at the C-7 position, stereochemistry at the C-7 position, the absence of phenyl group at the C-7 position. Flow cytometry data indicate that the cytotoxic effects of the synthesized analogues in a culture of K562 cells are mediated by apoptosis, additionally revealing that these molecules induced changes in cell cycle distribution of these cells. Results of Western blot analysis suggested that the most of synthesized compounds induce apoptosis in K562 cells in caspase-dependent way. [ABSTRACT FROM AUTHOR]

Aims The present study aimed to further investigate the anti-inflammatory activity of goniothalamin (GTN), a styryl lactone, as well as its antinociceptive effects. Main methods The anti-inflammatory activity was evaluated in models of paw edema induced by different mediators in mice and carrageenan-induced peritonitis. Evaluation of the antinociceptive effect was performed through acetic acid-induced writhing test and formalin test. Activity of GTN on gene expression levels of interleukin-1beta (IL-1β), induced nitric oxidase synthase (iNOS) and cyclooxygenase-2 (COX-2) were evaluated in vitro in lipopolysaccharide (LPS)-stimulated macrophage (RAW 264.7), as well as gene expression and protein levels of tumor necrosis factor-alpha (TNF-α). Key findings Pretreatment with GTN (300 mg/kg) significantly reduced paw edema induced by compound 48/80, prostaglandin E 2 , phospholipase A 2 and bradykinin. GTN (10, 30 and 100 mg/kg) inhibited leukocyte migration in the peritonitis model and gene expression levels of IL-1β, iNOS and TNF-α, as well as TNF-α protein levels, in LPS-stimulated macrophages, without affecting COX-2 gene expression levels. GTN inhibited nociception induced by acetic acid in the writhing model and in the formalin test, when both neurogenic and inflammatory phases were inhibited. Significance For the first time the acute anti-inflammatory profile of GTN is characterized and its antinociceptive activity reported. The current study shows that GTN inhibits both vascular and cellular phases of inflammation, with bradykinin and PLA 2 induced inflammation being the most affected by GTN. Its anti-inflammatory effects also involved the in vitro inhibition of gene expression of alarm cytokines and mediators as IL-1β, iNOS and TNF-α. [ABSTRACT FROM AUTHOR]

A divergent total synthesis of cytotoxic natural products (+)-crassalactones B ( 2 ) and C ( 3 ) has been achieved by utilizing diacetone d -glucose ( 4 ) as a chiral precursor. The key steps of the synthesis of both targets 2 and 3 were a stereo-selective addition of phenyl magnesium bromide to a dialdose derivative, a regioselective introduction of the cinnamic acid residue, and a stereospecific furano-lactone ring formation by cyclocondensation of a suitable hemiacetal derivative with Meldrum's acid. No protection is necessary for the synthesis of the (+)-crassalactone C ( 3 ), except the diacetonide function that is already present in the commercially available starting material 4 . Preparation of (+)-crassalactone B ( 2 ) from the same starting material, requires the use of a single silyl ether protecting group throughout the synthesis. The synthesized natural products were evaluated for their in vitro antiproliferative activity against PC3, HT29 and A549 human tumour cell lines. [ABSTRACT FROM AUTHOR]

The World Health Organization estimates that 4 billion people or 80 % of the population use plants for curative purposes or for their natural health benefits. Accordingly, biodiversity is an important source of active natural products especially used in traditional medicine as healers transmitted knowledge of traditional usage of medicinal plants from generation to generation whereas pharmacologically active compounds within remained obscure. The present review documents cytotoxicity and anti-cancer potential of known compounds of the Goniothalamus species from the Annonaceae family existing in tropical and subtropical Asia and being intensively used for medicinal purposes. [ABSTRACT FROM AUTHOR]

Abstract: An evaluation of Indonesian plants to identify compounds with immune modulating activity revealed that the methanolic extract of an Alphonsea javanica Scheff specimen possessed selective anti-inflammatory activity in a nuclear factor-kappa B (NF-κB) luciferase and MTT assay using transfected macrophage immune (Raw264.7) cells. A high-throughput LC/MS-ELSD based library approach of the extract in combination with the NF-κB and MTT assays revealed the styryl lactone (+)-altholactone (2) was responsible for the activity. Compound 2, its acetylated derivate (+)-3-O-acetylaltholactone (3), and the major compound of this class, (+)-goniothalmin (1), were further evaluated to determine their anti-inflammatory potential in the NF-κB assay. Concentration–response studies of 1–3 indicated that only 2 possessed NF-κB based anti-inflammatory activity. Compound 2 reduced the LPS-induced NO production, phosphorylation of IκBα, and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) using Western blot analysis. Further studies using qPCR indicated 2 reduced the expression of eight pro-inflammatory cytokines/enzymes (0.8–5.0μM) which included: COX-2, iNOS, IP-10, IL-1β, MCP-1, GCS-F, IL-6 and IFN-β. These results indicated that 2 displays broad spectrum immune modulating activity by functioning as an anti-inflammatory agent against LPS-induced NF-κB signaling. Conversely the selective cytotoxicity and in vivo anti-tumor and anti-inflammatory activity previously reported for 1 do not appear to arise from a mechanism that is linked to the NF-κB immune mediated pathway. [Copyright &y& Elsevier]

Abstract: Treatment of 7-O-benzoyl-5-O-benzyl derivatives of (+)-goniofufurone or 7-epi-(+)-goniofufurone with titanium(IV) chloride or titanium(IV) bromide gave 7-chloro and 7-bromo-7-deoxy-goniofufurone mimics as the main reaction products along with minor amounts of the corresponding C-7 epimers. An unexpected cyclized product, benzoxepane 8 was isolated in some cases. [Copyright &y& Elsevier]

Abstract: A short and efficient syntheses of goniothalesdiol A, leiocarpin A, and (+)-goniodiol are reported by a convergent strategy using tandem aminoxylation–allylation reaction as a key step starting from benzaldehyde. [Copyright &y& Elsevier]

An efficient total synthesis of (+)-goniodiol was illustrated by using Carreira alkynylation and Sharpless asymmetric dihydroxylation as key steps. [ABSTRACT FROM AUTHOR]

Abstract: An investigation of the chemical constituents in a dichloromethnae extract of Goniothalamus undulatus root led to the isolation of three known styryl lactones (5-acetoxyisogoniothalamin oxide, O-acetylaltholactone and altholactone), and four known annonaceous acetogenins (annonacin, cis-annonacin, goniothalamicin and cis-goniothalamicin). These compounds were subjected to a sulphorhodamine B (SRB) cytotoxicity assay against human large cell lung carcinoma (COR-L23), and normal human fetal fibroblast (MRC-5), cell lines. The isolated acetogenins showed higher cytotoxic activity against COR-L23 compared to the styryl lactones, with IC50 values in the range of 0.5–1.7μM and 7.4–15.4μM, respectively. A similar pattern of cytotoxicity was also observed against the other cell line (MRC-5); acetogenins IC50 values were in the range of 11.8–31.4μM, and those for styryl lactones were in the range of 48.7–102.8μM. This is the first report of a bioassay-guided isolation of chemical constituents from G. undulatus and on cytotoxic studies of the isolated compounds using these particular lung cancer cell lines. [Copyright &y& Elsevier]

The new styrylpyrone derivative, viz. 4-methoxy-3-methylgoniothalamin ( 1), and the known compound sulochrin were isolated from the marine-derived fungi Penicillium glabrum and P. implicatum. The structure of compound 1 was determined by X-ray diffraction, 2D NMR spectroscopy, and high-resolution mass spectrometry. It was shown for the first time that sulochrin increases expression of the protein Hsp70. [ABSTRACT FROM AUTHOR]

Abstract: This paper describes a straightforward divergent synthesis of (+)-goniofufurone mimics (4, 5 and 6) starting from d-xylose. In a preliminary bioassay, analogues 4 and 5 exhibited a submicromolar antiproliferative activity towards HL-60 cells, while the corresponding parent compound 1 was completely inactive against this cell line. At the same time, these molecules showed approximately 10-fold stronger cytotoxicity in the same cell line when compared to the standard anticancer drug doxorubicin (DOX). Analogue 6 displayed 18- and 3-fold higher potency in Raji cell line when compared to control compounds 1 and DOX, respectively. A new divergent route for the preparation of (+)-goniofufurone (1) and (+)-crassalactone C (3) from d-xylose is also disclosed. [Copyright &y& Elsevier]

Total synthesis of styryl lactone natural products cryptomoscatone D1, D2, and (5 R ,7 S )-kurzilactone has been accomplished in good yield from commercial available trans -cinnamaldehyde. The key steps involved in these syntheses are Mukaiyama aldol reaction, diastereoselective reduction, Brown’s allylation, and ring closing metathesis. [ABSTRACT FROM AUTHOR]

Abstract: (R)- and (S)-Goniothalamin (1) and analogues 2–9 were efficiently prepared in high overall yield and enantiomeric purity, and their cytotoxic activities were evaluated against eight human cancer cell lines. A structure–activity relationship study (SAR) allowed us to establish the relevant structural features for the cytotoxic activity of goniothalamin analogues. In addition, we have identified non-natural form of goniothalamin (S)-1 and analogue 5 as the highest and more selective cytotoxic compounds against kidney cancer cell growth (786-0) with IC50 =4 and 5nM, respectively, and compound 8 (IC50 =4nM) as the more potent against breast cancer cells with resistance phenotype for adryamycin (NCI.ADR). [Copyright &y& Elsevier]

Abstract: A simple and highly efficient stereoselective total synthesis of (+)-garvensintriol, isolated from the stem bark of Goniothalamus arvensis, is described using Sharpless kinetic resolution, MacMillan α-hydroxylation, and Horner–Wadsworth–Emmons olefination as the key steps. [Copyright &y& Elsevier]

Abstract: The synthesis of the styryl lactone Leiocarpin C has been achieved in a highly stereoselective manner using Jacobsen’s kinetic resolution, Sharpless asymmetric epoxidation and Sharpless asymmetric dihydroxylation as key steps. This is the first total synthesis of Leiocarpin C, and thus establishes for the first time the absolute stereochemistry of this natural product. [Copyright &y& Elsevier]

Phytochemical investigation on the stem bark of Goniothalamus tapis Miq. led to the isolation of seven known styryl-lactones, 3-acetyl-isoaltholactone (1), goniothalamin (2), isoaltholactone (3), cheliensisin A (4), 7- epi -goniofufurone (5), goniopypyrone (6), garvensintriol (7), and two steroids, stigmasterol (8) and β-sitosterol (9). The structures of all the compounds were elucidated based on the analysis of spectroscopic data and comparison with reported literature. The chemotaxonomic significance of all these compounds were summarized. Among all the styryl-lactones, compound 1 was isolated naturally from plant for the first time while compounds 4 , 5 and 7 have not been previously reported in Goniothalamus tapis Miq. Compound 2 was the first styryl-lactone isolated from many species of Goniothalamus including other families such as Cucurbitaceae, Lauraceae, Stemonaceae and Apocynaceae). Compounds 3 and 6 were found in ten species of Goniothalamus where the latter were also found in other genus (Polyalthia Blume). • Chemical constituents of Goniothalamus tapis were investigated. • The structures of compounds were confirmed through the spectroscopic data analysis. • 3-acetyl-isoaltholactone was isolated naturally from plant for the first time. • Compound 4 , 5 and 7 were isolated for the first time from G. tapis. [ABSTRACT FROM AUTHOR]

Malaria, a devastating infectious disease which was initially recognized as episodic fever, is caused by parasitic protozoan of the genus Plasmodium. Medicinal plants with ethnobotanical information to treat fever and/or malaria has been the key element in identifying potential plant candidates for antimalarial screening. Goniothalamus lanceolatus Miq. (Annonaceae) is used as a folk remedy, particularly to treat fever and skin diseases. In this context, supported with previous preliminary data of its antiplasmodial activity, this study was undertaken to determine the in vitro antiplasmodial and cytotoxicity activities of G. lanceolatus crude extracts and its major compounds. The in vitro antiplasmodial activity was determined by parasite lactate dehydrogenase (pLDH) assay on chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of Plasmodium falciparum. The cytotoxicity activity was evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on hepatocellular carcinoma (HepG2) and normal liver (WRL-68) cell lines. The root methanol extract possessed potent antiplasmodial activity against both P. falciparum 3D7 and K1 strains (IC 50 = 2.7 μg/ml, SI = 140; IC 50 = 1.7 μg/ml, SI = 236). Apart from the DCM extract of stem bark and root that were found to be inactive (IC 50 > 50 μg/ml) against 3D7 strain, all other tested crude extracts exhibited promising (5< IC 50 < 15 μg/ml) to moderate (15< IC 50 < 50 μg/ml) antiplasmodial activity against both strain. Additionally, only compound C (Parvistone D) exerted promising antiplasmodial activity against 3D7 strain (IC 50 = 7.5 μM, SI = 51) whereas compound A, B and D showed moderate antiplasmodial activity against the same strain (20 < IC 50 < 100 μM). Interestingly, when tested on K1 strain, compound A, C and D exhibited promising antiplasmodial activity (2 < IC 50 < 20 μM) while compound B exhibited moderate activity (IC 50 = 26.9 μM). Cytotoxicity study showed that all tested crude extracts and compounds were non-toxic on WRL-68 and HepG2 cell lines (CC 50 > 30 µg/ml, CC 50 > 10 µM, respectively), except for the hexane and DCM extracts of root, which exerted mild cytotoxicity on HepG2 cell line (IC 50 < 30 μg/ml). This study suggests that the root methanol extract and compound C (Parvistone D) obtained from G. lanceolatus are highly potential for exploitation as source of antimalarial agents. Parvistone D is identified as one of the bioactive styryl lactones found in the plant extract. It is also noteworthy, that the extract and compound were more active against chloroquine-resistant (K1) strain of P. falciparum. Further studies are being carried out to assess their toxicity profile and antimalarial efficacy in animal model. Image 1 [ABSTRACT FROM AUTHOR]

This review covers the chemistry and biological aspects of goniothalamin-related styryl lactones isolated from natural sources. This family of secondary metabolites has been reported to display diverse uses in folk medicine, but only a limited number of these compounds have been throughly investigated regarding their biological profile. Herein, we cover the goniothalamin-related styryl lactones having a C6-C3-C4 framework which appeared in the literature for the first time in the period 2000-2017, and the reports on the synthesis, biological activity and mechanism of action which were published from 2007-2017., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)