Highly Enantioselective Lewis Acid Catalyzed Conjugate Addition of Imidazo[1,2-a]pyridines to α,ß-Unsaturated 2-Acylimidazoles under Mild Conditions.

A highly enantioselective protocol for the conjugate addition of 2-arylimidazo[1,2-a]pyridines and other imidazo derivatives to α,ß-unsaturated 2-acylimidazoles is described. The method uses a previously reported chiral-at-metal rhodium catalyst and provides the corresponding adducts in yields of 25-98% with enantioselectivities up to er > 99:1. Additionally, the transformation proceeds under mild conditions using ethanol as the solvent at room temperature.

The Antinociceptive Effect of a Hydroalcoholic Extract of Polygala altomontana and Its Chemical Profile Using UPLC-ESI-QTOF-HR-MS.

The hydroalcoholic extract of Polygala altomontana (30, 100, and 300 mg/kg, i.g.) showed a dose-dependent antinociceptive action during the inflammatory phase of the formalin test. In addition, the preparation (30 and 300 mg/kg, i.g.) showed anti-hyperalgesic action when tested on a mechanical nociception model. UPLC-ESI-QTOF-MS data indicated the active extract contained phenylpropanoid sucrose esters, glycosylated quercetin derivatives, styrylpyrones, and coumarins. Some identified compounds, including styrylpyrones and coumarins, have previously demonstrated antinociceptive action. The results also show that P. altomontana shows potential for developing pain-relieving herbal remedies and drugs.

Studies of Cytotoxicity Effects, SARS-CoV-2 Main Protease Inhibition, and in Silico Interactions of Synthetic Chalcones.

SARS-CoV-2 main protease (Mpro ) plays an essential role in proteolysis cleavage that promotes coronavirus replication. Thus, attenuating the activity of this enzyme represents a strategy to develop antiviral agents. We report inhibitory effects against Mpro of 40 synthetic chalcones, and cytotoxicity activities, hemolysis, and in silico interactions of active compounds. Seven of them bearing a (E)-3-(furan-2-yl)-1-arylprop-2-en-1-one skeleton (10, 28, and 35-39) showed enzyme inhibition with IC50 ranging from 13.76 and 36.13 µM. Except for 35 and 36, other active compounds were not cytotoxic up to 150 µM against THP-1 and Vero cell lines. Compounds 10, and 35-39 showed no hemolysis while 28 was weakly hemotoxic at 150 µM. Moreover, molecular docking showed interactions between compound 10 and Mpro (PDBID 5RG2 and 5RG3) with proximity to cys145 and His41, suggesting a covalent binding. Products of the reaction between chalcones and cyclohexanethiol indicated that this binding could be a Michael addition type.

Inhibitory effects of 190 compounds against SARS-CoV-2 Mpr o protein: Molecular docking interactions.

COVID-19 has caused many deaths since the first outbreak in 2019. The burden on healthcare systems around the world has been reduced by the success of vaccines. However, population adherence and the occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are still challenging tasks to be affronted. In addition, the newly approved drug presents some limitations in terms of side effects and drug interference, highlighting the importance of searching for new antiviral agents against SARS-CoV-2. The SARS-CoV-2 main protease (Mpr o ) represents a versatile target to search for new drug candidates due to its essential role in proteolytic activities responsible for the virus replication. In this work, a series of 190 compounds, composed of 27 natural ones and 163 synthetic compounds, were screened in vitro for their inhibitory effects against SARS-CoV-2 Mpro . Twenty-five compounds inhibited Mpro with inhibitory constant values (Ki ) between 23.2 and 241 µM. Among them, a thiosemicarbazone derivative was the most active compound. Molecular docking studies using Protein Data Bank ID 5RG1, 5RG2, and 5RG3 crystal structures of Mpro revealed important interactions identified as hydrophobic, hydrogen bonding and steric interactions with amino acid residues in the active site cavity. Overall, our findings indicate the described thiosemicarbazones as good candidates to be further explored to develop antiviral leads against SARS-CoV-2. Moreover, the studies showed the importance of careful evaluation of test results to detect and exclude false-positive findings.

Semisynthetic Sesquiterpene Lactones Generated by the Sensibility of Glaucolide B to Lewis and Brønsted-Lowry Acids and Bases: Cytotoxicity and Anti-Inflammatory Activities.

Sesquiterpene lactone (SL) subtypes including hirsutinolide and cadinanolide have a controversial genesis. Metabolites of these classes are either described as natural products or as artifacts produced via the influence of solvents, chromatographic mobile phases, and adsorbents used in phytochemical studies. Based on this divergence, and to better understand the sensibility of these metabolites, different pH conditions were used to prepare semisynthetic SLs and evaluate the anti-inflammatory and antiproliferative activities. Therefore, glaucolide B (1) was treated with various Brønsted-Lowry and Lewis acids and bases-the same approach was applied to some of its derivatives-allowing us to obtain 14 semisynthetic SL derivatives, 10 of which are hereby reported for the first time. Hirsutinolide derivatives 7a (CC50 = 5.0 µM; SI = 2.5) and 7b (CC50 = 11.2 µM; SI = 2.5) and the germacranolide derivative 8a (CC50 = 3.1 µM; SI = 3.0) revealed significant cytotoxic activity and selectivity against human melanoma SK-MEL-28 cells when compared with that against non-tumoral HUVEC cells. Additionally, compounds 7a and 7c.1 showed strongly reduced interleukin-6 (IL-6) and nitrite (NOx) release in pre-treated M1 macrophages J774A.1 when stimulated with lipopolysaccharide. Despite the fact that hirsutinolide and cadinanolide SLs may be produced via plant metabolism, this study shows that acidic and alkaline extraction and solid-phase purification processes can promote their formation.

Anti-inflammatory and anti-aggregating effects of rangpur in the first trimester of growth: ultra-performance liquid chromatography-electrospray mass spectrometry profile and quantification of hesperidin.

BACKGROUND: Citrus fruits are a rich source of valuable molecules, and their industrial processing produces bagasses, little explored to generate important by-products. These Citrus residues, including seeds and peels, also contain numerous pharmacologically important substances. To reduce the impact of these Citrus by-products, young, harvested fruits could be used as a functional supplemental food while another part is grown until maturity for industrial production. This study therefore aims to valorize rangpur (Citrus limonia) in the first 3 months of its growth by investigating and comparing its monthly chemical profiles using ultra-performance liquid chromatography-electrospray mass spectrometry (UPLC-ESI-MS) and its anti-inflammatory and antiplatelet activity. RESULTS: Extracts obtained from the fruits harvested in November, December, and January, 2017 and 2018 (L221117, L161217, and L160118) showed different UPLC-ESI-MS profiles. Twenty-five of the 26 detected metabolites were identified as cyclitol, pyrrolidine betaine, aryl propanoyl esters, chlorogenic acids, flavonoids, coumarins, and limonoids. Quantification studies indicated an increased concentration of hesperidin from the younger fruits to the older fruits of the series. L160118 reduced nitrogen oxide (NOx), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6) levels more than other extracts. Their activity followed the same trends as the hesperidin concentration in each fruit. In contrast, the most promising antiplatelet activity was observed with the extracts from the two youngest fruits. This suggests combined effects of the chemical components found in these fruits' extracts. CONCLUSION: The extracts obtained from these young fruits showed considerable anti-inflammatory and antiplatelet activity. Overall, young rangpur could be used as raw material to produce functional foods without producing any waste. © 2022 Society of Chemical Industry.

In silico and in vitro degradation studies of isolated phloroglucinols eugenial C and eugenial D from Eugenia umbelliflora fruits.

INTRODUCTION: Eugenia umbelliflora fruits are an important source of phloroglucinols, as eugenial C and eugenial D, related to antimicrobial activity against Staphylococcus aureus. However, for the establishment of new antimicrobial substances, it is essential to know their stability profile, in view of driving the administration route and the release system development. METHODOLOGY: The in silico approaches, based on the Fukui indices and bond dissociation analysis, were performed. Eugenial C and eugenial D, isolated from the green fruits of E. umbelliflora, with purity > 90%, were submitted to stress degradation including: acid (0.5 mM hydrochloric acid) and alkaline (0.5 mM sodium hydroxide) hydrolysis, and oxidation (0.25% hydrogen peroxide), in different periods, monitoring by high-performance liquid chromatography with ultraviolet detector (HPLC-UV). Eugenial C was also submitted to UV-visible radiation (2,400 lux/h) and dry/humid heating (40°C, 75% relative humidity). RESULTS: In silico studies indicated that both molecules have regions of high susceptibility to nucleophilic and electrophilic attack as well as sites likely to suffer auto-oxidation. Under in vitro tests, both phloroglucinols proved to be very unstable under hydrolysis (eugenial C and D were degraded 23.8% and 89.0% in acid and 78.4% and 97.8% in alkaline conditions, respectively) and oxidation (eugenial C and D degraded 31.9% and 28.6%, respectively), both during 5 min. Eugenial C degraded 12.6% and 63.8% under dry and humid heat, respectively, without photosensitivity. CONCLUSION: The in vitro stress tests monitored by HPLC-UV were in agreement with in silico degradation prediction. Phloroglucinols could be unstable if administered by oral route and also under environmental conditions demanding a protective release system.

NOx-, IL-1ß-, TNF-α-, and IL-6-Inhibiting Effects and Trypanocidal Activity of Banana (Musa acuminata) Bracts and Flowers: UPLC-HRESI-MS Detection of Phenylpropanoid Sucrose Esters.

Banana inflorescences are a byproduct of banana cultivation consumed in various regions of Brazil as a non-conventional food. This byproduct represents an alternative food supply that can contribute to the resolution of nutritional problems and hunger. This product is also used in Asia as a traditional remedy for the treatment of various illnesses such as bronchitis and dysentery. However, there is a lack of chemical and pharmacological data to support its consumption as a functional food. Therefore, this work aimed to study the anti-inflammatory action of Musa acuminata blossom by quantifying the cytokine levels (NOx, IL-1ß, TNF-α, and IL-6) in peritoneal neutrophils, and to study its antiparasitic activities using the intracellular forms of T. cruzi, L. amazonensis, and L. infantum. This work also aimed to establish the chemical profile of the inflorescence using UPLC-ESI-MS analysis. Flowers and the crude bract extracts were partitioned in dichloromethane and n-butanol to afford four fractions (FDCM, FNBU, BDCM, and BNBU). FDCM showed moderate trypanocidal activity and promising anti-inflammatory properties by inhibiting IL-1ß, TNF-α, and IL-6. BDCM significantly inhibited the secretion of TNF-α, while BNBU was active against IL-6 and NOx. LCMS data of these fractions revealed an unprecedented presence of arylpropanoid sucroses alongside flavonoids, triterpenes, benzofurans, stilbenes, and iridoids. The obtained results revealed that banana inflorescences could be used as an anti-inflammatory food ingredient to control inflammatory diseases.

Cytotoxicity, antiprotozoal, and anti-inflammatory activities of eight curry powders and comparison of their UPLC-ESI-QTOF-MS chemical profiles.

BACKGROUND: Curry powder is a blend of spices that is extensively consumed worldwide and mainly in Central Asia. Its preparation is strictly related to each locality and, because of the health benefits of its constituents, eight commercial forms of this condiment were biologically and chemically investigated. This study aimed to compare their chemical profile as well as their anti-inflammatory, cytotoxic, and antiparasitic activities. RESULTS: Curry samples 1 and 7 inhibited leukocyte influx and myeloperoxidase activity, while only 7 was active on protein exudate and NOx species. 2, 6, and 8 displayed trypanocidal effect against Trypanosoma cruzi amastigote, whereas 6 showed antileishmanial activity on Leishmania amazonensis amastigote. 2, 6, and 8 also inhibited the growth of THP-1 cells used as the parasite's host. Among the cytotoxic samples (4 and 6), curry sample 6 induced apoptosis in MDA-MB-231 cells. Nevertheless, 4 and 6 were unselectively cytotoxic to non-tumoral and tumoral cells. The anti-inflammatory, cytotoxicity, and antiparasitic assays were respectively performed by carrageenan-induced pleurisy test, Alamar blue assay, and intracellular parasite-host cell model. Ultra-performance liquid chromatographic-electrospray ionization mass spectrometric data from the spices revealed both similar and different metabolites in their composition. CONCLUSION: The results obtained indicate that different formulations can contribute different health benefits as a result of their chemical composition. © 2018 Society of Chemical Industry.

In vitro antibacterial and antibiotic modifying activity of crude extract, fractions and 3',4',7-trihydroxyflavone from Myristica fragrans Houtt against MDR Gram-negative enteric bacteria.

BACKGROUND: Nutmeg is the seed kernel inside the fruit of Myristica fragrans Houtt. (Myristicaceae). It possesses various pharmacological activities but is used in Cameroon only for its flavor in making cakes. The present study thus aimed to investigate the in vitro antibacterial activity and antibiotic modifying activities of crude seed kernel methanol extract (MFS), fractions (MFSa-e) as well as 3',4',7-trihydroxyflavone from Myristica fragrans against a panel of multi-drug resistant (MDR) Gram-negative bacteria. METHODS: The modified rapid p-iodonitrotetrazolium chloride (INT) colorimetric assay was used to determine the Minimal Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) on the tested bacteria, as well as those of antibiotics in association with the extract and/or isolated compound. Column chromatography was used for the fractionation and purification of the seed kernel extract whilst the chemical structures of compounds were determined using spectroscopic techniques. RESULTS: Phytochemical investigations lead to the isolation of 3',4',7-trihydroxyflavone from the fraction MFSb. The crude extract showed antibacterial activity with MICs ranging from 32 to 1024 µg/mL on the majority of the 29 tested Gram-negative bacterial strains. Fraction MFSb inhibited the growth of 100% (29/29) of the tested bacterial strains, as well as the compound 3',4',7-trihydroxyflavone (12/12) with a MIC values ranging from 32 to 1024 µg/mL, and 4 to 128 µg/mL respectively. The lowest MIC value (4 µg/mL) was recorded with 3',4',7-trihydroxyflavone against Providencia stuartii ATCC299645 as well as the best MBC value (16 µg/mL) against the same strain. In the presence of Phenylalanine-Arginine-ß-Naphthylamide (PAßN), an efflux pumps inhibitor, the activity of the extract increased on 73.33% (11/15) meanwhile that of 3',4',7-trihydroxyflavone increased on 100% tested bacteria. The compound 3',4',7-trihydroxyflavone potentiated the activity of antibiotics in the majority of the tested bacterial strains. CONCLUSION: The results of the present work provide additional information on the use of nutmeg and it major antibacterial component, 3',4',7-trihydroxyflavone, as a potential drug in the treatment of bacterial infections including multidrug resistant phenotypes.

Prospecting for cytotoxic and antiprotozoal 4-aryl-4H-chromenes and 10-aryldihydropyrano[2,3-f]chromenes.

Different studies reported that genetic predisposition or metabolic dysfunction are the risk factors for cancer. Infectious parasitic diseases were listed among factors that predispose to cancer. Because of the resemblance between the life cycle of cancer cells and some parasites, this study aimed to prepare pyran derivatives with cytotoxic and antiprotozoal potencies. Therefore, 7 chromenes, 10 pyranocoumarins, and an unexpected intermediate were obtained from a multi-reagent one-pot reaction. These compounds were evaluated for their cytotoxicity on sensitive and resistant leukemia cancer cells lines and against two protozoan parasites, namely Trypanosoma cruzi and Leishmania amazonensis amastigote. Promising cytotoxicity (IC50 values of less than 1 µM) was obtained for two of the synthetic products (12 and 15). Compound 12 induced apoptosis and cell cycle arrest in CCRF-CEM leukemia cells in G0/G1 while compound 15 and doxorubicin induced apoptosis and arrest in the S and G2/M phases. Ten of these products showed trypanocidal activity, while only five of them were weakly active on L. amazonensis. Three of the obtained pyrans showed significant cytotoxicity and antitrypanocidal activity, simultaneously. Nevertheless, all antiparasitic compounds revealed potency with low selectivity toward THP-1 cells used as host.

UPLC-ESI-QTOF-MS2 characterisation of Cola nitida resin fractions with inhibitory effects on NO and TNF-α released by LPS-activated J774 macrophage and on Trypanosoma cruzi and Leishmania amazonensis.

INTRODUCTION: The resin of Cola nitida is used in western Cameroon as incense for spiritual protection and during ritual ceremonies. This plant secretion has never been investigated although previous chemical and biological studies on other resins have drawn many attentions. OBJECTIVE: The resin fractions which revealed inhibitory effect on nitric oxide (NO) and tumour necrosis factor alpha (TNF-α) released by lipopolysaccharide (LPS)-activated J774 macrophage as well as on intracellular forms of Leishmania amazonensis and Trypanosoma cruzi amastigote were chemically characterised. Moreover, their antiparasitic activities were compared to those of semi-synthetic triterpenes. METHODOLOGY: The anti-inflammatory activity was evaluated by measuring the nitrite production and the TNF-α concentration in the supernatants of LPS-activated macrophages by antigen capture enzyme-linked immunosorbent assay. Moreover, the antiparasitic assay was performed by infecting the host cells (THP-1) in a ratio parasite/cell 10:1 (L. amazonensis) and 2:1 (T. cruzi) and then exposed to the samples. The resin was separated in vacuo by liquid chromatography because of its sticky behaviour and the chemical profiles of the obtained fractions (F1-F4) were established by dereplication based on UPLC-ESI-MS2 data while semi-synthetic triterpenes were prepared from α-amyrin by oxidation reactions. RESULTS: Fractions F1-F4 inhibited NO and TNF-α almost similarly. However, only F1, F3 and F4 showed promising antiparasitic activities while F2 was moderately active against both parasites. Hence, F1-F4 were exclusively composed of pentacyclic triterpenes bearing oleanane and ursane skeletons. Semi-synthetic compounds revealed no to moderate antiparasitic activity compared to the fractions. CONCLUSION: Although it will be difficult to prove the interaction resin-spirit, interesting bioactivities were found in the resin fractions.

Unravelling the biosynthesis of pyriculol in the rice blast fungus Magnaporthe oryzae.

Pyriculol was isolated from the rice blast fungus Magnaporthe oryzae and found to induce lesion formation on rice leaves. These findings suggest that it could be involved in virulence. The gene MoPKS19 was identified to encode a polyketide synthase essential for the production of the polyketide pyriculol in the rice blast fungus M. oryzae. The transcript abundance of MoPKS19 correlates with the biosynthesis rate of pyriculol in a time-dependent manner. Furthermore, gene inactivation of MoPKS19 resulted in a mutant unable to produce pyriculol, pyriculariol and their dihydro derivatives. Inactivation of a putative oxidase-encoding gene MoC19OXR1, which was found to be located in the genome close to MoPKS19, resulted in a mutant exclusively producing dihydropyriculol and dihydropyriculariol. By contrast, overexpression of MoC19OXR1 resulted in a mutant strain only producing pyriculol. The MoPKS19 cluster, furthermore, comprises two transcription factors MoC19TRF1 and MoC19TRF2, which were both found individually to act as negative regulators repressing gene expression of MoPKS19. Additionally, extracts of ΔMopks19 and ΔMoC19oxr1 made from axenic cultures failed to induce lesions on rice leaves compared to extracts of the wild-type strain. Consequently, pyriculol and its isomer pyriculariol appear to be the only lesion-inducing secondary metabolites produced by M. oryzae wild-type (MoWT) under these culture conditions. Interestingly, the mutants unable to produce pyriculol and pyriculariol were as pathogenic as MoWT, demonstrating that pyriculol is not required for infection.

Anti-inflammatory tetraquinane diterpenoids from a Crinipellis species.

The small pro-inflammatory 10kDa chemokine CXCL10 (Interferon-inducible protein 10, IP-10) plays an important role in mediating immune responses through the activation and recruitment of leukocytes such as T cells, eosinophils, monocytes and NK cells to the sites of inflammation. Elevated levels of CXCL10 have been associated with chronic inflammatory and infectious diseases and therefore CXCL10 represents an attractive target for the development of new anti-inflammatory drugs. In a search for anti-inflammatory compounds from fungi inhibiting the inducible CXCL10 promoter activity, four new tetraquinane diterpenoids, crinipellin E (1), crinipellin F (2), crinipellin G (3) and crinipellin H (4) were isolated from fermentations of a Crinipellis species. The structures of the compounds were elucidated by a combination of one- and two-dimensional NMR spectroscopy and mass spectrometry. Compounds 1, 2, and 3 inhibited the LPS/IFN-γ induced CXCL10 promoter activity in transiently transfected human MonoMac6 cells in a dose-dependent manner with IC50 values of 15µM, 1.5µM, and 3.15µM respectively, whereas compound 4 was devoid of any biological activity. Moreover, compounds 1, 2 and 3 reduced mRNA levels and synthesis of pro-inflammatory mediators such as cytokines and chemokines in LPS/IFN-γ stimulated MonoMac6 cells.

Antibacterial activities of the methanol extract, fractions and compounds from Elaeophorbia drupifera (Thonn.) Stapf. (Euphorbiaceae).

BACKGROUND: Elaeophorbia drupifera (Thonn.) Stapf. (Euphorbiaceae) is used in Cameroonian folk medicine to treat several ailments including bacterial-related diseases such as skin infections. In this study, the methanol extract from the leaves (EDL), fractions (EDLa-d), sub-fractions EDLc1-7 and EDLc31-35 as well as isolated compounds were tested for their antimicrobial activities against a panel of Gram-negative and Gram-positive bacteria including multidrug resistant (MDR) phenotypes. METHODS: The broth microdilution method was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the above samples; column chromatography was used for the fractionation and purification of the leaves extract whilst the chemical structures of compounds were determined using spectroscopic techniques. RESULTS: Phytochemical investigation lead to the isolation of a mixture (1:3) of stigmasterol and ß-sitosterol (1 + 2), euphol (3), sitosterol-O-ß- D -xylopyranoside (4), 3,3',4'-tri-O-methylellagic acid (5), a mixture (1:1) of afzelin and quercetin-3-O-ß-D-xylopyranoside (6 + 7), 3,3',4'-tri-O-methylellagic acid 4-O-ß-D-glucopyranoside (8), ellagic acid-4-O-ß-xylopyranoside-3,3',4'-trimethyl ether (9) from EDLc. Crude extract and fractions displayed selective activities with MIC values ranged from 32 to 1024 µg/mL for EDL against 84.9% of the 33 tested bacteria, 93.9% for EDLc, 69.7% for EDLb, 33.4% for EDLa and 0.03% for EDLd. MIC values ranged from 16 to 1024 µg/mL were obtained with EDLc3 and EDLc4 on all tested bacteria meanwhile other sub-fractions displayed selective activities. MIC value of 32 µg/mL was obtained with fractions EDLa against Escherichia coli AG100, EDLc against Enterobacer aerogenes ATCC13048 and EA298. For sub-fractions obtained from EDLc, the lowest MIC value of 16 µg/mL was recorded with EDLc3 against Staphylococcus aureus MRSA11. A corresponding value of 8 µg/mL against Providencia stuartii NAE16 was recorded with EDLc33 obtained from further fractionation of EDLc3. EDLc3 had MIC values below 100 µg/mL against all tested bacteria. Compound 5 as well as the mixture (1:1) of 6 and 7 inhibited the growth of all the tested bacteria with MICs ranged from 64 to 256 µg/mL. CONCLUSION: Elaeophorbia drupifera is a potential source of phytomedicine to tackle MDR bacteria. Sub-fraction EDLc3 was more active than all isolated compounds and deserves further investigations to develop natural drug to combat Gram-negative, Gram-positive bacteria and otherwise MDR phenotypes.

ESI-MS2 and Anti-inflammatory Studies of Cyclopropanic Triterpenes. UPLC-ESI-MS and MS2 Search of Related Metabolites from Donella ubanguiensis.

INTRODUCTION: Triterpenes are one of the largest secondary metabolites groups spread in the plant kingdom with various skeletons. These metabolites have showed various bioactivities including anti-inflammatory activity. OBJECTIVE: The study aims to explore the mass spectrometry fragmentation of donellanic acids A-C (DA A-C), three compounds identified from Donella ubanguiensis; in addition, the fragmentation behaviour of these metabolites will serve as a fingerprint to search and characterise triterpenes congeners in fruits, bark and wood crude extracts of D. ubanguiensis. This work was prompted by the anti-inflammatory activity on leukocyte migration, exudate concentrations and myeloperoxidase activity obtained for DA A-B. METHODOLOGY: The bioactivity was performed on mouse model of pleurisy induced by carrageenan and the parameters were analysed by veterinarian automated cell counter and colorimetric assays. While the tandem mass analyses of DA A-C were carried out by a direct infusion ESI-QTOF-MS/MS, the extracts were studied by UPLC-ESI-QTOF-MS and UPLC-ESI-QTOF-MS/MS. RESULTS: DA A displayed interesting anti-inflammatory activity by inhibiting leukocyte migration, exudate concentrations and myeloperoxidase activity (p < 0.05) while DA B was weakly active (p > 0.05). Moreover, the diagnostic of the MS2 behaviour of DA A-C in conjunction with the chromatograms and the obtained MS2 data of the crude extract led to the characterisation of three cyclopropane triterpenes (T1-T3) and six saponins (T4-T9) from the fruits, the bark, and the wood extracts. CONCLUSIONS: Donella species deserve more investigation since metabolites related to the anti-inflammatory compound (DA A) could be identified. Copyright © 2016 John Wiley & Sons, Ltd.

A new member of the fusaricidin family - structure elucidation and synthesis of fusaricidin E.

Two hitherto unknown fusaricidins were obtained from fermentation broths of three Paenibacillus strains. After structure elucidation based on tandem mass spectrometry and NMR spectroscopy, fusaricidin E was synthesized to confirm the structure and the suggested stereochemistry. The synthesis was based on a new strategy which includes an efficient access to the 15-guanidino-3-hydroxypentadecanoyl (GHPD) side chain from erucamide.

Total Synthesis of (-)-Hymenosetin.

The 3-decalinoyltetramic acid (-)-hymenosetin and its N-methyl analogue were prepared in 11 and 8 steps, respectively, from (+)-citronellal using an intramolecular Diels-Alder reaction as the key step. This method represents the first example for the synthesis of a 3-decalinoyltetramic acid with a free NH moiety. The stereochemistry of the title compound, an unnatural diastereomer, and of a decalin building block was studied in detail using circular dichroism spectroscopy in the IR and UV/VIS freqeuncy range. This allowed to determine the absolute configuration of the natural product and to plan the synthetic route.

Individual and combined antiparasitic effect of six plant metabolites against Leishmania amazonensis and Trypanosoma cruzi.

Six plant metabolites including isobavachalcone (1), 4-hydroxylonchocarpine (2), and (E)-1-(2,2-dimethyl-2H-chromen-6-yl)-3-(4-hydroxyphenyl)prop-2-en-1-one (3), 6,8-(di-3-methyl-but-2-enyl)eriodictyol (4), damnacanthal (5), and buesgenine (6) were evaluated for their leishmanicidal and trypanocidal activities against intracellular amastigotes of Leishmania amazonensis and Trypanosoma cruzi. Compounds 2-4 and 6 displayed antileishmanial activity while 3 and 5 showed trypanocidal effect. The leishmanicidal activity of 6 was expressed with the lowest IC50 (5.70µg/mL) whereas the most trypanocidal metabolite (5) showed its activity with IC50 at 11.14µg/mL. In addition, antiprotozoal effect of mixtures of 1-6 prepared at different ratios (3:1, 1:1, and 1:3) was also investigated. Interestingly, 1 and 2 initially inactive against T. cruzi, displayed trypanocidal activities when mixed together. This activity increased when 3 (13.63µg/mL) was combined with 1 in ratios 1:1 (10.01µg/mL) and 3:1 (7.78µg/mL). Moreover, the leishmanicidal effect of 4 against L. amazonensis increased in the mixture 6/4 (1:3).

Terphenyl Derivatives from Allantophomopsis lycopodina.

Three secondary fungal metabolites 1-3 with a benzo[b]naphtho[2,1-d]furan skeleton were isolated from submerged cultures of the ascomycete Allantophomopsis lycopodina. The NMR-based structure elucidation was challenging due to a low H/C ratio of only 0.64 and 0.68, respectively. NMR measurements in two different solvents and the use of NMR experiments such as HSQC-TOCSY and LR-HSQMBC proved to be helpful in this respect. The proposed structures obtained from the comprehensive analysis of the NMR data were verified by comparison of recorded and computed NMR chemical shifts from quantum chemical calculations of several constitutional isomers and were further analyzed with the aid of the DP4 and DP4+ probabilities.