Green electrospun Janus membrane of polyether block amide (PEBA) doped with hierarchical magnesium hydrogen phosphate for the removal of pharmaceuticals and personal care products.

It has been a challenge to prepared polyether block amide (PEBA) fibrous membrane via solution electrospinning. The only few reported methods though involved hazardous solvents and surfactants which were against the principle of green chemistry. In this work, uniform fibrous membrane of PEBA was successfully fabricated by solution electrospinning with a bio-based solvent dihydrolevoglucosenone (Cyrene). To further improve the mechanical strength and adsorption performance of the PEBA membrane, a hierarchical magnesium hydrogen phosphate (MgHPO4·1.2H2O, MHP) was synthesized to blend evenly into the PEBA matrix. A Janus MHP/PEBA membrane with one side of hydrophobic surface and the other side of hydrophilic surface was subsequently prepared, which exhibited fast adsorption, high capacity, good selectivity and reusability towards ibuprofen, acetaminophen, carbamazepine and triclosan. In addition, the Janus membrane showed high removal efficiency of the above contaminants in secondary wastewater effluent with good long term stability. It demonstrated that this Janus MHP/PEBA membrane had a good potential in practical wastewater treatment.

Amide alkaloids and neolignans from Piper hongkongense and their inhibitory activities of PCSK9 expression.

Four undescribed amide alkaloids hongkongensines A-C and 1-(1-oxo-6-hydroxy-2E,4E-dodecadienyl)-piperidine, five known amide alkaloids, and three known neolignans were isolated from the aerial part of Piper hongkongense. The planar structures of these compounds were determined by detailed analyses of HR-ESI-MS and NMR data. The absolute configurations of hongkongensines A-C were elucidated by single-crystal X-ray diffraction analysis and ECD calculations. Moreover, the inhibitory activities of PCSK9 expression in vitro for all compounds were assessed by PCSK9 AlphaLISA screening. Kadsurenone (10) displayed a significant inhibitory activity at 5 µM with an inhibition rate of 51.98%, compared with 55.55% of berberine (BBR 5 µM).

Chemical Constituents from the Heartwood of Solanum Verbascifolium L. And Their Anti-Inflammatory Activities Combined Network Pharmacology.

Phytochemical studies on 95 % ethanol extract of the heartwood of Solanum verbascifolium L. resulted in the isolation of one new amide derivative (1), and 21 known phenylpropanoids compounds. The structures were characterized by spectral analysis and high-resolution mass spectrometric analysis. The anti-inflammatory activity of amide compounds 1-4 and 6-9 by investigating their impact on the release of nitric oxide (NO) in MH-S cells. Our findings unveiled significant inhibitory effects on NO secretion. Compound 1 exhibited robust dose-dependent suppression, with pronounced inhibition observed at both 20 µM (P<0.01) and 40 µM (P<0.01). Furthermore, compound 9 demonstrated noteworthy inhibitory effects at 40 µM (P<0.01). Similarly, compounds 3 and 4 displayed substantial inhibition of NO secretion at the same concentration, although the significance level was slightly lower (P<0.05). It is expected that there is a substantial association between the anti-inflammatory activities of amides and their targets, specifically PTGS2, by combining network pharmacology and molecular docking techniques. This discovery emphasizes amides' potential as an interesting subject for additional study in the realm of anti-inflammatory medications.

New Analogues of Amides and Quinolinones Produced by Streptomyces sp. YIM S01983.

Streptomide (1), a new amide analogue, streptomynone (2), a new quinolinone, and ten known compounds including three aliphatic acids (3-5), two amides (6-7), four cyclic dipeptides (8-11), and an adenosine (12) were isolated from the fermentation broth of Streptomyces sp. YIM S01983 isolated from a sediment sample collected in Bendong Village, Huadong Town, Chuxiong, China. Their structures were determined by analysis of the 1D/2D-NMR and HR-ESI-MS spectra. Compound 12 presented weak antimicrobial activities against Candida albicans and Aligenes faecalis (MIC=64 µg/mL). Compounds 7 and 12 showed weak cytotoxic activity against MHCC97H.

Undescribed Lignanamide and Flavone C-Glucoside Isolated from the Aerial Parts of Piper Samentosum with NO Production Inhibitory Activity in LPS Activated RAW 264.7†Cells.

In this study, two undescribed compounds (1 and 2), together with eight known compounds (3-10) were isolated from the aerial parts of Piper samentosum by various chromatography methods. Their chemical structures were determined to be 7'''-oxolyciumamide N (1), vitexin 2''-O-ß-D-(6'''-feruloyl)-glucopyranoside (2), 1,2-dihydro-6,8-dimethoxy-7-hydroxy-1-(3,4-dihydroxyphenyl)-N1,N2-bis-[2-(-hydroxyphenyl)ethyl]-2,3-napthalene dicarboamide (3), vitexin 6''-O-ß-D-glucopyranoside (4), vitexin 2''-O-α-L-rhamnopyranoside (5), methyl 2-hydroxybenzoate-2-O-ß-D-apiofuranosyl-(1→2)-O-ß-D-glucopyranoside (6), ficuside G (7), methyl 2-O-ß-D-glucopyranosylbenzoate (8), methyl 2,5-dihydroxybenzoate-5-O-ß-D-glucopyranoside (9), and 3,7-dimethyloct-1-ene-3,6,7-triol 6-O-ß-D-glucopyranoside (10) by spectroscopic data analysis including HR-ESI-MS, 1D-, and 2D-NMR spectra. Compounds 1-5 inhibited nitric oxide production in LPS-stimulated RAW264.7 macrophages with the IC50 values of 27.62, 74.03, 38.54, 70.39, and 44.95 µM, respectively. The NMR data of 9 were firstly reported herein.

Highly Concentrated Linear Guanidine Amides from the Marine Sipunculid Phascolosoma granulatum.

The chemical diversity of annelids, particularly those belonging to the class Sipuncula, remains largely unexplored. However, as part of a Marine Biodiscovery program in Ireland, the peanut worm Phascolosoma granulatum emerged as a promising source of unique metabolites. The purification of the MeOH/CH2Cl2 extract of this species led to the isolation of six new linear guanidine amides, named phascolosomines A-F (1-6). NMR analysis allowed for the elucidation of their structures, all of which feature a terminal guanidine, central amide linkage, and a terminal isobutyl group. Notably, these guanidine amides were present in unusually high concentrations, comprising ∼3% of the dry mass of the organism. The primary concentration of the phascolosomines in the viscera is similar to that previously identified in linear amides from sipunculid worms and marine fireworms. The compounds from sipunculid worms have been hypothesized to be toxins, while those from fireworms are reported to be defensive irritants. However, screening of the newly isolated compounds for inhibitory bioactivity showed no significant inhibition in any of the assays conducted.

Bursatella leachii Purple Ink Secretion Concentrate Exerts Cytotoxic Properties against Human Hepatocarcinoma Cell Line (HepG2): In Vitro and In Silico Studies.

Liver cancer is a leading cause of cancer death globally. Marine mollusc-derived drugs have gained attention as potential natural-based anti-cancer agents to overcome the side effects caused by conventional chemotherapeutic drugs during cancer therapy. Using liquid chromatography-mass spectrometry, the main biomolecules in the purple ink secretion released by the sea hare, named Bursatella leachii (B. leachii), were identified as hectochlorin, malyngamide X, malyngolide S, bursatellin and lyngbyatoxin A. The cytotoxic effects of B. leachii ink concentrate against human hepatocarcinoma (HepG2) cells were determined to be dose- and time-dependent, and further exploration of the underlying mechanisms causing the programmed cell death (apoptosis) were performed. The expression of cleaved-caspase-8 and cleaved-caspase-3, key cysteine-aspartic proteases involved in the initiation and completion of the apoptosis process, appeared after HepG2 cell exposure to the B. leachii ink concentrate. The gene expression levels of pro-apoptotic BAX, TP53 and Cyclin D1 were increased after treatment with the B. leachii ink concentrate. Applying in silico approaches, the high scores predicted that bioactivities for the five compounds were protease and kinase inhibitors. The ADME and cytochrome profiles for the compounds were also predicted. Altogether, the B. leachii ink concentrate has high pro-apoptotic potentials, suggesting it as a promising safe natural product-based drug for the treatment of liver cancer.

Menthol-assisted homogenous liquid-liquid microextraction for HPLC/UV determination of favipiravir as an antiviral for COVID-19 in human plasma.

Favipiravir is a promising antiviral agent that has been recently approved for treatment of COVID-19 infection. In this study, a menthol-assisted homogenous liquid-liquid microextraction method has been developed for favipiravir determination in human plasma using HPLC/UV. The different factors that could affect the extraction efficiency were studied, including extractant type, extractant volume, menthol amount and vortex time. The optimum extraction efficiency was achieved using 300 µL of tetrahydrofuran, 30 mg of menthol and vortexing for 1 min before centrifuging the sample for 5 min at 3467g. Addition of menthol does not only induce phase separation, but also helps to form reverse micelles to facilitate extraction. The highly polar favipiravir molecules would be incorporated into the hydrophilic core of the formed reverse micelle to be extracted by the non-polar organic extractant. The method was validated according to the FDA bioanalytical method guidelines. The developed method was found linear in the concentration range of 0.1 to 100 µg/mL with a coefficient of determination of 0.9992. The method accuracy and precision were studied by calculating the recovery (%) and the relative standard deviation (%), respectively. The recovery (%) was in the range of 97.1-103.9%, while the RSD (%) values ranged between 2.03 and 8.15 %. The developed method was successfully applied in a bioequivalence study of Flupirava® 200 mg versus Avigan® 200 mg, after a single oral dose of favipiravir administered to healthy adult volunteers. The proposed method was simple, cheap, more eco-friendly and sufficiently sensitive for biomedical application.

Hydroxycinnamic Acid Amide Dimers from Goji Berry and Their Potential Anti-AD Activity.

Three undescribed hydroxycinnamic acid amide dimers 1-3 were isolated and identified from an extract of Goji berry. Their molecular structures were elucidated based on NMR, MS, and IR spectra analysis. Compounds 1-3 were hydroxycinnamic acid amide dimers, which possess a cyclic butane moiety formed by head-to-head connection. These compounds at 25 µM showed the disaggregation potency on the copper-mediated Aß1-42 aggregation ranging from 27.3±3.2 to 31.0±2.9 %. This study provides new information on the antiaging traditional usage of goji berry.

Separation and characterization of phenylamides from Piper kadsura using preparative supercritical fluid chromatography and ultra-high-performance supercritical fluid chromatography-tandem mass spectrometry.

A preparative supercritical fluid chromatography method for the separation of Piper kadsura obtained five phenylamide compounds, which had the same structural skeleton, but changed in the number and position of methoxyl substituents. To improve the separation selectivity of these structural analogues, silica, phenyl, and chiral stationary phases were screened. Only through the combination of Chiral C and phenyl columns could the separation of the five phenylamides be solved. The two-step strategy using preparative supercritical fluid chromatography presented good orthogonality that ensured the purity of the phenylamides. Then, an ultra-high-performance supercritical fluid chromatography hyphened tandem mass spectrometry method was developed, and the fragmentation pattern of phenylamides was summarized. It mainly cleaved in the amide bond to produce the fragment ion, which could help to judge the substituent positions. Twenty-eight possible molecular weights of hydroxyl and methoxyl substituted phenylamides were calculated and screened. Nine compounds were extracted in three [M + H]+ ions at m/z 284.13, 314.13, and 344.13, including five purified compounds and the other four positional or trans-cis phenylamide isomers in low content. The methods developed in this research were useful in the separation and characterization of phenylamide analogues.

Two amide glycosides from Portulaca oleracea L. and its bioactivities.

Two novel amide glycosides, named oleraciamide E (1) and oleraciamide F (2), were isolated from the Portulaca oleracea L. Their structures were determined by means of 1D and 2D NMR spectroscopic and UHPLC-ESI-TOF-MS methods. Oleraciamide E (1) exhibited anticholinesterase activity with IC50 values of 52.43 ± 0.33 µM, and presented scavenging activity in 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical quenching assay, with the IC50 values of 24.64 ± 0.33 µM.

Electron attachment to isolated and microhydrated favipiravir.

Electron attachment and its equivalent in complex environments, single-electron reduction, are important in many biological processes. Here, we experimentally study the electron attachment to favipiravir, a well-known antiviral agent. Electron attachment spectroscopy is used to explore the energetics of associative (AEA) and dissociative (DEA) electron attachment to isolated favipiravir. AEA dominates the interaction and the yields of the fragment anions after DEA are an order of magnitude lower than that of the parent anion. DEA primary proceeds via decomposition of the CONH2 functional group, which is supported by reaction threshold calculations using ab initio methods. Mass spectrometry of small favipiravir-water clusters demonstrates that a lot of energy is transferred to the solvent upon electron attachment. The energy gained upon electron attachment, and the high stability of the parent anion were previously suggested as important properties for the action of several electron-affinic radiosensitizers. If any of these mechanisms cause synergism in chemo-radiation therapy, favipiravir could be repurposed as a radiosensitizer.

New amide alkaloids and carbazole alkaloid from the stems of Clausena lansium.

Five unreported alkaloids including four amide alkaloids (1a, 2a, 3a, and 3b) and one carbazole alkaloid (4) with two known compounds (1b, 2b) were obtained from the stems of Clausena lansium. Their structures were demonstrated by spectroscopic experiments. And the absolute configurations of compounds 1a, 1b, 2b, and 3b were determined by single X-ray diffraction analysis. The neuroprotection assay showed that compound 4 had moderate inhibition effect on PC12 cells induced by serum withdrawal at the concentration of 10 µM. And compounds 1a and 4 had weak protective effects on primary neurons against oxygen glucose deprivation injury at the concentration of 10 µM.

Stixilamides A and B, two new phenolic amides from the leaves of Stixis suaveolens.

The ethylacetate extracts produced from the leaves of Stixis suaveolens (Roxb.) was characterized on the basis of NMR spectra combined with extensive mass spectroscopic techniques. The chemical characterization revealed presence of two new phenolic amides which were named as stixilamides A and B.

Tricholomines A and B, two new amides from the fruiting bodies of Tricholoma bakamatsutake.

Two new amides tricholomines A (1) and B (2), along with nine known compounds, were isolated from the dried fruiting bodies of Tricholoma bakamatsutake. Their structures were determined on the basis of extensive spectroscopic analysis or comparison with the data in the literatures. The absolute configuration of 1 was confirmed by single crystal X-ray diffraction analysis.

Phenolamides: Plant specialized metabolites with a wide range of promising pharmacological and health-promoting interests.

Phenolamides constitute a family of metabolites, widely represented in the plant kingdom, that can be found in all plant organs with a predominance in flowers and pollen grains. They represent a large and structurally diverse family, resulting from the association of phenolic acids with aliphatic or aromatic amines. Initially revealed as active compounds in several medicinal plant extracts, phenolamides have been extensively studied for their health-promoting and pharmacological properties. Indeed, phenolamides have been shown to exhibit antioxidant, anti-inflammatory, anti-cancer and antimicrobial properties, but also protective effects against metabolic syndrome and neurodegenerative diseases. The purpose of this review is to summarise this large body of literature, including in vitro and in vivo studies, by describing the diversity of their biological properties and our actual knowledge of the molecular mechanisms behind them. With regard to their considerable pharmacological interest, the question of industrial production is also tackled through chemical and biological syntheses in engineered microorganisms. The diversity of biological activities already described, together with the active discovery of the broad structural diversity of this metabolite family, make phenolamides a promising source of new active compounds on which future studies should be focused.

Oxepinamide F biosynthesis involves enzymatic D-aminoacyl epimerization, 3H-oxepin formation, and hydroxylation induced double bond migration.

Oxepinamides are derivatives of anthranilyl-containing tripeptides and share an oxepin ring and a fused pyrimidinone moiety. To the best of our knowledge, no studies have been reported on the elucidation of an oxepinamide biosynthetic pathway and conversion of a quinazolinone to a pyrimidinone-fused 1H-oxepin framework by a cytochrome P450 enzyme in fungal natural product biosynthesis. Here we report the isolation of oxepinamide F from Aspergillus ustus and identification of its biosynthetic pathway by gene deletion, heterologous expression, feeding experiments, and enzyme assays. The nonribosomal peptide synthase (NRPS) OpaA assembles the quinazolinone core with D-Phe incorporation. The cytochrome P450 enzyme OpaB catalyzes alone the oxepin ring formation. The flavoenzyme OpaC installs subsequently one hydroxyl group at the oxepin ring, accompanied by double bond migration. The epimerase OpaE changes the D-Phe residue back to L-form, which is essential for the final methylation by OpaF.

Applying a Chemogeographic Strategy for Natural Product Discovery from the Marine Cyanobacterium Moorena bouillonii.

The tropical marine cyanobacterium Moorena bouillonii occupies a large geographic range across the Indian and Western Tropical Pacific Oceans and is a prolific producer of structurally unique and biologically active natural products. An ensemble of computational approaches, including the creation of the ORCA (Objective Relational Comparative Analysis) pipeline for flexible MS1 feature detection and multivariate analyses, were used to analyze various M. bouillonii samples. The observed chemogeographic patterns suggested the production of regionally specific natural products by M. bouillonii. Analyzing the drivers of these chemogeographic patterns allowed for the identification, targeted isolation, and structure elucidation of a regionally specific natural product, doscadenamide A (1). Analyses of MS2 fragmentation patterns further revealed this natural product to be part of an extensive family of herein annotated, proposed natural structural analogs (doscadenamides B-J, 2-10); the ensemble of structures reflect a combinatorial biosynthesis using nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) components. Compound 1 displayed synergistic in vitro cancer cell cytotoxicity when administered with lipopolysaccharide (LPS). These discoveries illustrate the utility in leveraging chemogeographic patterns for prioritizing natural product discovery efforts.

Gano oil: A novel antinociceptive agent extracted from Ganoderma lucidum inhibits paw oedema and relieves pain by hypnotic and analgesic actions of fatty acid amides.

ETHNOPHARMACOLOGICAL RELEVANCE: Lingzhi or Reishi - Ganoderma lucidum (Fr.) P. Karst is an extensively used medicinal mushroom in folklore and traditional medicine in south East Asia to treat a number of diseases. Lingzhi is known as 'mushroom of immortality' in Chinese folklore. In Traditional Chinese Medicine it is considered as a panacea to cure all diseases. AIM OF THE STUDY: This study aims to evaluate antinociceptive effect of Gano oil, a novel fatty acid rich extract obtained from G. lucidum and identification of the active principle. MATERIALS & METHODS: Gano oil extracted from Ganoderma lucidum was evaluated for inhibition of formalin-induced paw oedema on Swiss albino mice by oral administration as well as topical application. Antinociceptive activity of Gano oil was tested by acetic acid - induced abdominal writhing test as well as hot plate test. Free radical scavenging activity was determined by DPPH assay. COX enzyme inhibiting activity was assayed using different concentrations of Gano oil exposed to LPS stimulated RAW 264.7 cell line. NF-kB inhibiting activity of Gano oil was assayed using Lentix-293T P65 Ds Red stable cell line by fluorescent imaging and flow cytometry analysis. Chemical profile of Gano oil was ascertained by HPTLC analysis and active principle was identified by HRLCMS analysis. RESULTS: The oral administration of Gano oil at doses of 10,25, 50 mg/kg b.wt showed 42, 58 and 73% inhibition of paw oedema while topical applications at dose of 1,5 and 10% reduced 33, 50 and 58% oedema respectively. Acetic acid writhing test showed that Gano oil inhibited 44.44% contortions (p < 0.001) and while in hot plate method Gano oil at 25 mg/kg b. wt showed response latency of 30.0 ±â€¯2.08 s for 120 min compared to base 1.65 ±â€¯0.32 s (p < 0.01). Gano oil at 100 µg/ml inhibited 50% COX enzyme activity (p < 0.01). High throughput flurescent imaging and flow cytometry assay revealed marked ability of Gano oil to inhibit NF-kB activity. Gano oil was found to possess dose dependent free radical scavenging activity as evident from DPPH assay. HPTLC analysis of Gano oil indicated the chemical figure print. HR LC-MS analysis showed the major chemical components were fatty acid amides namely, Oleamide, C18H35NO, M+281, Hexadecanamide, C16H33NO, M+255 and 9-oxo-10 (E) Octadecadienoic acid, C18H30O3 M+294. CONCLUSION: Fatty acid rich Gano oil extracted from G.lucidum is a novel antinociceptive agent capable to inhibit oedema by oral administration as well as topical application. The results indicate the pharmacological interest, clinical significance and therapeutic use. The finding suggests that Gano oil might be a potent natural product based analgesic. The effect might be assigned to the fatty acid amide constituents especially oleamide which has been demonstrated to have analgesic and hypnotic actions.

Anti-inflammatory and antiproliferative prenylated sulphur-containing amides from the leaves of Glycosmis pentaphylla.

Glycosmis pentaphylla (Retz.) DC (Rutaceae) has been traditionally considered as anti-cancer and anti-inflammatory medicine. However, active compounds of sulphur-containing amides remain largely unknown. In the present work, eighteen previously undescribed sulphur-containing amides (1-18) and three known analogues (19-21) were isolated from the leaves of G. pentaphylla. Their structures were elucidated by NMR spectroscopy and mass spectrometry. All isolated prenylated sulphur-containing amides were evaluated for their anti-inflammatory properties together with antiproliferative activities in vivo. Prenylated sulphur-containing amides exhibited significant inhibitory effects against nitric oxide (NO) production stimulated by lipopolysaccharide in mouse macrophage RAW 264.7 cells with the IC50 values ranging from 0.16 ± 0.10 to 16.74 ± 2.81 µM. Meanwhile, sulphur-containing amides also exhibited considerable antiproliferative activities against HepG2 cell line with IC50 values ranging from 7.47 ± 0.91 to 16.23 ± 0.80 µM. These findings enrich and improve the research on the structural diversity and biological activity of sulphur-containing amides and provide phytochemical and pharmacological evidence for the further development and utilization of the leaves of G. pentaphylla in pharmaceutical industry.