Investigation of the marine sponge Agelas dispar MeOH fractions using feature-based molecular networking, dereplication, and isolation led to the discovery of new bromopyrrole-derived metabolites. An ...in-house library of bromopyrrole alkaloids previously isolated from A. dispar and Dictyonella sp. was utilized, along with the investigation of an MS/MS fragmentation of these compounds. Our strategy led to the isolation and identification of the disparamides A–C (1–3), with a novel carbon skeleton. Additionally, new dispyrins B–F (4–8) and nagelamides H2 and H3 (9 and 10) and known nagelamide H (11), citrinamine B (12), ageliferin (13), bromoageliferin (14), and dibromoageliferin (15) were also isolated and identified by analysis of spectroscopic data. Analysis of MS/MS fragmentation data and molecular networking analysis indicated the presence of hymenidin (16), oroidin (17), dispacamide (18), monobromodispacamide (19), keramadine (20), longamide B (21), methyl ester of longamide B (22), hanishin (23), methyl ester of 3-debromolongamide B (24), and 3-debromohanishin (25). Antibacterial activity of ageliferin (13), bromoageliferin (14), and dibromoageliferin (15) was evaluated against susceptible and multi-drug-resistant ESKAPE pathogenic bacteria Klabsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterococcus faecalis. Dibromoageliferin (15) displayed the most potent antimicrobial activity against all tested susceptible and MDR strains. Compounds 13–15 presented no significant hemolytic activity up to 100 μM.
In this study, Ru(II)-arene complexes with acylthiourea ligands of the type Ru(η6‑p‑cymene)(PPh3)(T)ClPF6(1–5) and Ru(η6‑p‑cymene)(PPh3)(T)PF6(1a, 4a), where PPh3 = triphenylphosphine and ...T = N‑acyl‑N′(monosubstituted)thiourea, were synthesized and characterized, and their cytotoxic properties were also evaluated. 1a and 4a were obtained from the hydrolysis reaction of 1 and 4. All complexes showed unusual coordination modes for acylthiourea ligands, which are coordinated in a monodentate fashion (S) in 1–5, while they found to be bidentate (S,N), in 1a and 4a. To the best of our knowledge, 1a and 4a are the first crystallographically reported ruthenium compounds with acylthiourea coordinated via S and N(amide) atoms. The cytotoxicity of the compounds was evaluated in human lung cells, A549 and MRC-5. The IC50 values ranging from 0.25 to 0.61 μM after 48 h incubation in lung cancer cells indicate that the compounds showed high cytotoxicity with values significantly lower than the reference drug, cisplatin (11.84 μM). Interaction studies were carried out using human serum albumin (HSA) and DNA. All complexes showed similar cytotoxic activity, however complex 1a, which is the hydrolysis product of 1, presented the highest activity and selectivity among all seven compounds synthesized here. Complexes 1 and 1a inhibited the colony formation decreasing the colony size and inducing morphology changes in A549 cells. These complexes induced apoptosis cell death and promoted cell cycle arrest in the Sub-G1 phase with a decrease in the cell number at the S phase.
Ru(II)-arene complexes with acylthiourea ligands showed unusual coordination modes, either (S)-monodentate or (S,N)-bidentate, where the latter is the hydrolysis product of the former coordination situation. Two complexes are the first crystallographically ruthenium compounds with acylthiourea coordinated via S,N(amide) atoms. All complexes showed expressive cytotoxicity, interact with DNA and induced apoptosis. Display omitted
•Ru(II)-Arene complexes with acylthiourea ligands displaying unusual coordination modes•First crystallographical report of Ru/acylthiourea complex coordinated via S/N atoms•IC50 values significantly lower than cisplatin•Complexes/DNA interaction via minor groove and induction of apoptosis
The potential of NMR spectroscopy to differentiate honeys concerning to the nectar employed in its production was evaluated. The application of chemometric methods to 1H NMR spectra has allowed to ...discriminate the honeys produced in the state of São Paulo, being identified the signals of responsible substances for the discrimination. Application of PCA and HCA methods to 1H NMR data have resulted in the natural clustering of the samples. Wildflower honeys were characterized by higher concentration of phenylalanine and tyrosine. Citrus honeys showed higher amounts of sucrose than other compounds, while eucalyptus honeys had higher amount of lactic acid than the others. Assa-peixe honeys showed spectra similar to eucalyptus and citrus. Sugar-cane honeys showed some signals similar to eucalyptus and citrus honeys, but also showed the tyrosine and phenylalanine signals. Adulterated honeys showed 5-hydroxymethylfurfural, citric acid and ethanol signals. KNN, SIMCA and PLS-DA methods were used to build predictive models for honey classification. In the commercial honeys prediction KNN, SIMCA and PLS-DA models correctly classified 66.7; 22.2 and 72.2% of the samples, respectively.
► Chemometrics and NMR were used to classify honeys according to their nectar origin. ► PLS-DA showed better efficiency to classify the honeys. ► PCA and HCA allowed discriminating and detecting adulterated honeys. ► NMR spectra and loading graphics showed compounds responsible by honeys discrimination.
Chiral molecules in nature are involved in many biological events; their selectivity and specificity make them of great interest for understanding the behavior of bioactive molecules, by providing ...information about the chiral discrimination. Inspired by these conformational properties, we present the design and synthesis of novel chiral platinum(II) complexes featuring phosphine and chloroquine ligands with the general formula PtCl(P)2(CQ)PF6 (where (P)2 = triphenylphosphine (PPh3) (5), 1,3-bis(diphenylphosphine)propane (dppp) (6), 1,4-bis(diphenylphosphine)butane (dppb) (7), 1,1′-bis(diphenylphosphine)ferrocene (dppf) (8), and CQ = chloroquine and their precursors of the type PtCl2(P)2 are described. The complexes were characterized by elemental analysis, absorption spectroscopy in the infrared and ultraviolet–visible (UV-vis) regions, multinuclear (1H, 13C, 31P, 15N, and 195Pt) NMR spectroscopy, cyclic voltammetry, and mass spectrometry (in the case of chloroquine complexes). The interactions of the new platinum–chloroquine complexes with both albumin (BSA), using fluorescence spectroscopy, and DNA, by four widely reported methods were also evaluated. These experiments showed that these Pt-CQ complexes interact strongly with DNA and have high affinities for BSA, in contrast to CQ and CQDP (chloroquine diphosphate), which interact weakly with these biomolecules. Additional assays were performed in order to investigate the cytotoxicity of the platinum complexes against two healthy cell lines (mouse fibroblasts (L929) and the Chinese hamster lung (V79-4)) and four tumor cell lines (human breast (MDA-MB-231 and MCF-7), human lung (A549), and human prostate (DU-145)). The results suggest that the Pt-CQ complexes are generally more cytotoxic than the free CQ, showing that they are promising as anticancer drugs.
Studies of secondary metabolites (natural products) that cover their isolation, chemical synthesis and bioactivity investigation present myriad opportunities for discovery. For example, the isolation ...of novel secondary metabolites can inspire advances in chemical synthesis strategies to achieve their practical preparation for biological evaluation. In the process, chemical synthesis can also provide unambiguous structural characterization of the natural products. Although the isolation, chemical synthesis and bioactivity studies of natural products are mutually beneficial, they are often conducted independently. Here, we demonstrate the benefits of a collaborative study of the phomactins, diterpenoid fungal metabolites that serve as antagonists of the platelet activating factor receptor. Our isolation of novel phomactins has spurred the development of a bioinspired, unified approach that achieves the total syntheses of six congeners. We also demonstrate in vitro the beneficial effects of several phomactins in suppressing the rate of repopulation of tumour cells following gamma radiation therapy.
Ruthenium(II) complexes (Ru1–Ru5), with the general formula Ru(N-S)(dppe)2PF6, bearing two 1,2-bis(diphenylphosphino)ethane (dppe) ligands and a series of mercapto ligands (N-S), have been ...developed. The combination of these ligands in the complexes endowed hydrophobic species with high cytotoxic activity against five cancer cell lines. For the A549 (lung) and MDA-MB-231 (breast) cancer cell lines, the IC50 values of the complexes were 288- to 14-fold lower when compared to cisplatin. Furthermore, the complexes were selective for the A549 and MDA-MB-231 cancer cell lines compared to the MRC-5 nontumor cell line. The multitarget character of the complexes was investigated by using calf thymus DNA (CT DNA), human serum albumin, and human topoisomerase IB (hTopIB). The complexes potently inhibited hTopIB. In particular, complex Ru(dmp)(dppe)2PF6 (Ru3), bearing the 4,6-diamino-2-mercaptopyrimidine (dmp) ligand, effectively inhibited hTopIB by acting on both the cleavage and religation steps of the catalytic cycle of this enzyme. Molecular docking showed that the Ru1–Ru5 complexes have binding affinity by active sites on the hTopI and hTopI-DNA, mainly via π-alkyl and alkyl hydrophobic interactions, as well as through hydrogen bonds. Complex Ru3 displayed significant antitumor activity against murine melanoma in mouse xenograph models, but this complex did not damage DNA, as revealed by Ames and micronucleus tests.
Anthracnose is a crop disease usually caused by fungi in the genus Colletotrichum or Gloeosporium. These are considered one of the main pathogens, causing significant economic losses, such as in ...peppers and guarana. The current forms of control include the use of resistant cultivars, sanitary pruning and fungicides. However, even with the use of some methods of controlling these cultures, the crops are not free of anthracnose. Additionally, excessive application of fungicides increases the resistance of pathogens to agrochemicals and cause harm to human health and the environment. In order to find natural antifungal agents against guarana anthracnose, endophytic fungi were isolated from Amazon guarana. The compounds piliformic acid and cytochalasin D were isolated by chromatographic techniques from two Xylaria spp., guided by assays with Colletotrichum gloeosporioides. The isolated compounds were identified by spectrometric techniques, as NMR and mass spectrometry. This is the first report that piliformic acid and cytochalasin D have antifungal activity against C. gloeosporioides with MIC 2.92 and 2.46μmolmL−1 respectively. Captan and difenoconazole were included as positive controls (MIC 16.63 and 0.02μmolmL−1, respectively). Thus, Xylaria species presented a biotechnological potential and production of different active compounds which might be promising against anthracnose disease.
The structure of the fungal metabolite roussoellatide (1) has been established by spectroscopic and X-ray diffraction analyses. Results from feeding experiments with 1-13Cacetate, 2-13Cacetate, and ...1,2-13Cacetate were consistent with a biosynthetic pathway to the unprecedented skeleton of 1 involving Favorskii rearrangements in separate pentaketides, subsequently joined via an intermolecular Diels–Alder reaction.
Inspiratory muscle training (IMT) is known to promote physiological benefits and improve physical performance in endurance sports activities. However, the metabolic adaptations promoted by different ...IMT prescribing strategies remain unclear. In this work, a longitudinal, randomized, double-blind, sham-controlled, parallel trial was performed to investigate the effects of 11 weeks (3 days·week−1) of IMT at different exercise intensities on the serum metabolomics profile and its main regulated metabolic pathways. Twenty-eight healthy male recreational cyclists (30.4 ± 6.5 years) were randomized into three groups: sham (6 cm·H2O of inspiratory pressure, n = 7), moderate-intensity (MI group, 60% maximal inspiratory pressure (MIP), n = 11) and high-intensity (HI group, 85–90% MIP, n = 10). Blood serum samples were collected before and after 11 weeks of IMT and analyzed by 1H NMR and UHPLC-HRMS/MS. Data were analyzed using linear mixed models and metabolite set enrichment analysis. The 1H NMR and UHPLC-HRMS/MS techniques resulted in 46 and 200 compounds, respectively. These results showed that ketone body metabolism, fatty acid biosynthesis, and aminoacyl-tRNA biosynthesis were upregulated after IMT, while alpha linolenic acid and linoleic acid metabolism as well as biosynthesis of unsaturated fatty acids were downregulated. The MI group presented higher MIP, Tryptophan, and Valine levels but decreased 2-Hydroxybutyrate levels when compared to the other two studied groups. These results suggest an increase in the oxidative metabolic processes after IMT at different intensities with additional evidence for the upregulation of essential amino acid metabolism in the MI group accompanied by greater improvement in respiratory muscle strength.
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•The bioactive molecules’ delivery into the wound site improves the healing process.•The nanofibers possess attractive properties to act as drug delivery system.•The antimicrobial ...molecules loaded into nanofibers to avoid infections are described.•The bioactive molecules loaded into nanofibers to assist healing process are listed.•The changes induced on nanofibers’ structural/biological properties are overviewed.
Nowadays, despite the intensive research performed in the area of skin tissue engineering, the treatment of skin lesions remains a big challenge for healthcare professionals. In fact, none of the wound dressings currently used in the clinic is capable of re-establishing all the native features of skin. An ideal wound dressing must confer protection to the wound from external microorganisms, chemical, and physical aggressions, as well as promote the healing process by stimulating the cell adhesion, differentiation, and proliferation. In recent years different types of wound dressings (such as films, hydrocolloids, hydrogels, micro/nano fibers) have been developed. Among them, electrospun nanofibrous membranes due to their intrinsic properties like high surface area-to-volume ratio, porosity and structural similarity with the skin extracellular matrix have been regarded as highly promising for wound dressings applications. Additionally, the nanofibers available in these membranes can act as drug delivery systems, which prompted the incorporation of biomolecules within their structure to prevent skin infections as well as improve the healing process. In this review, examples of different bioactive molecules that have been loaded on polymeric nanofibers are presented, highlighting the antibacterial biomolecules (e.g. antibiotics, silver nanoparticles and natural extracts-derived products) and the molecules capable of enhancing the healing process (e.g. growth factors, vitamins, and anti-inflammatory molecules).
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