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Candida spp. are common opportunistic microorganisms in the human body and can cause mucosal, cutaneous, and systemic infections, mainly in individuals with weakened immune systems. Candida albicans is the most isolated and pathogenic species; however, multi-drug-resistant yeasts like Candida auris have recently been found in many different regions of the world. The increasing development of resistance to common antifungals by Candida species limits the therapeutic options. In light of this, the present review attempts to discuss the significance of marine natural products in controlling the proliferation and metabolism of C. albicans and non-albicans species. Natural compounds produced by sponges, algae, sea cucumber, bacteria, fungi, and other marine organisms have been the subject of numerous studies since the 1980s, with the discovery of several products with different chemical frameworks that can inhibit Candida spp., including antifungal drug-resistant strains. Sponges fall under the topmost category when compared to all other organisms investigated. Terpenoids, sterols, and alkaloids from this group exhibit a wide array of inhibitory activity against different Candida species. Especially, hippolide J, a pair of enantiomeric sesterterpenoids isolated from the marine sponge Hippospongia lachne, exhibited strong activity against Candida albicans, Candida parapsilosis, and Candida glabrata. In addition, a comprehensive analysis was performed to unveil the mechanisms of action and synergistic activity of marine products with conventional antifungals. In general, the results of this review show that the majority of chemicals derived from the marine environment are able to control particular functions of microorganisms belonging to the Candida genus, which can provide insights into designing new anti-candidal therapies.

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The chemical investigation of the fresh flowers of Albizia lebbeck (L.) Benth. (Fabaceae, Mimosoideae) led to the isolation of two new echinocystic acid saponins. They were isolated by using chromatographic methods and their structures were elucidated by detailed 1H and 13C NMR spectral data including 2 D-NMR (COSY, HSQC, HMBC and APT) spectroscopic techniques, high-resolution electrospray ionization mass spectrometry (HRESIMS) and acid hydrolysis. Their structures were established as 16-hydroxy-3-[[O-ß-D-xylopyranosyl-(1→2)-O-α-L-arabinopyranosyl-(1→6)-2-(acetylamino)-2-deoxy-ß-D-glucopyranosyl]oxy]-(3ß,16α)-olean-12-en-28-oic acid O-6-deoxy-α-L-mannopyranosyl-(1→4)-O-6-deoxy-α-L-mannopyranosyl-(1→2)-ß-D-glucopyranosyl ester (1) and 16-hydroxy-3-[[O-ß-D-xylopyranosyl-(1→2)-O-α-L-arabinopyranosyl-(1→6)-2-(acetylamino)-2-deoxy-ß-D-glucopyranosyl]oxy]-(3ß,16α)-olean-12-en-28-oic acid 6-O-[(2S,3R,4R)-tetrahydro-3-hydroxy-4-(hydroxymethyl)-2-furanyl]-ß-D-glucopyranosyl ester (2). Additionally, the permeability property and the capacity of interaction with biological membranes of compounds 1 and 2 were investigated.

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Ten previously undescribed metabolites were isolated from Peperomia incana (Haw.) A. Dietr. (Piperaceae), among which four contained a chromene moiety, two were identified as meroterpene lactones, and four were cannabinoid-like compounds. While the chemical structures of the compounds were assigned based on HRESIMS and 1D and 2D-NMR spectra analyses, the relative and absolute configurations were assigned from NOE correlations and a combination of ECD data and X-ray single crystal analyses, respectively. In a cytotoxic assay against a panel of seven human cancer cell lines (A549, MDA-MB-231, HeLa, DU 145, 5637, Hep G2, and MIA PaCa-2, which represent non-small cell lung cancer, as well as breast, cervical, prostate, bladder, liver, and pancreas carcinomas, respectively) most of the isolated compounds showed promising cytotoxic activities. The incanachromenes B, and incanabinoids A and C exhibited the highest cytotoxicity toward all tested cancer cell lines with IC50 values in the range of 5.0-10.0 µM, whereas incanolides A, B, and incanabinoid B showed the lowest cytotoxic activity. In addition, incanachromene C and incanabinoid C produced a significant antibacterial effect toward planktonic cells and biofilms of multidrug-resistant Staphylococcus aureus strains.

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The combination of computational methods and experimental data from Nuclear Magnetic Resonance (NMR) is a considerably valuable tool in the elucidation of new natural product structures and, also, in the structural revision of previously reported compounds. Until recently, only classical statistical parameters were used, for example, linear correlation coefficient (R2 ), mean absolute error (MAE), or root mean square deviation (RMSD), as a way to statistically "validate" the structure pointed out by experimental NMR spectra. Regarding the resolution of the relative configuration of organic molecules, novel tools were available in the last few years to assist in the NMR elucidation process. The most relevant are DP4+, which is based on a Bayesian probability, and ANN-PRA, which is based on artificial neural networks. The combined application of these tools has become the most accurate and important alternative to solve structural and stereochemical problems in natural product chemistry. Therefore, herein, in this case study, we intended to promote these novel tools, exploring the strengths and limitations of each approach in resolving the relative configuration of the sesquiterpene alpha-bisabol. We also highlighted the advantages of the complementary use of H- and C-DP4+ to obtain optimal results in the differentiation of the stereoisomers, validating the proposal with ANN-PRA method.

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Chemically cross-linked polyacrylontrile polymer gels, have been prepared as an alignment medium compatible with DMSO-d6. These gels allow measurement of residual dipolar couplings (RDCs) and residual chemical shift anisotropies (RCSAs) with good accuracy as tested with brucine and α-santonin natural compounds. The gels can be reversibly compressed allowing easy measurement of RCSAs. They also present good physical homogeneity, clean HSQC spectra with little background 1H signals, and allow unambiguous referencing of 13C spectra for RCSA extraction.

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Two new secondary metabolites, kongiilines A and B (1, 7), and two asperphenamate derivatives, asperphenamates B and C (5-6), together with 16 known compounds (2-4, 8-20), were isolated from Tibetan Plateau fungi Penicillium kongii and Penicillium brasilianum. This is the first report on asperphenamates B and C as naturally occurring compounds, and that aspterric acid is isolated from P. brasilianum for the first time. Their structures were elucidated by different spectroscopic techniques including high-resolution electrospray ionisation mass spectrum, 1D nuclear magnetic resonance (NMR), and 2D NMR as well as electronic circular dichroism. Compounds 4, 5, and 10 exhibited cytotoxicity activities against human colon carcinoma HCT116 cell line with IC50 values of 88.16, 77.68, and 36.92 µM, respectively. Fungi from Tibetan Plateau represent important and rich resources for the investigation of new chemicals.

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Seven anthraquinones were isolated from aerial parts of Heterophyllaea lycioides (Rusby) Sandwith (Rubiaceae), including three derivatives that have not been described before: a hetero-bianthraquinone identified as (R)-2-hydroxymethyl-2'methyl-1,1',6,6'-tetrahydroxy-5,5' bianthraquinone (lycionine), and two mono-chlorinated derivatives related to soranjidiol. One of them is a homo-bianthraquinone: (R)-7-chloro-2,2'-dimethyl-1,1',6,6'-tetrahydroxy-5,5' bianthraquinone (7-chlorobisoranjidiol), whereas the second halogenated derivative corresponds to a monomeric structure: 5-chloro-1,6-dihydroxy-2-methyl anthraquinone (5-chlorosoranjidiol). The four known compounds were already isolated from another species of this genus, H. pustulata, and they were identified as 5,5'-bisoranjidiol, soranjidiol, pustuline and heterophylline. Structural elucidation was performed by means of an extensive spectroscopic analysis, including 1D and 2D NMR data as well as by HRMS analysis. Chemical structures of 7-chlorobisoranjidiol and 5-chlorosoranjidiol were confirmed by their synthesis from 5,5'-bisoranjidiol and soranjidiol, respectively. Type I photosensitizing properties (superoxide anion radical generation, O2-) were assessed by using the nitroblue tetrazolium assay. When lycionine and chlorinated derivatives were irradiated, they enhanced the O2- production with respect to the control; 7-chlorobisoranjidiol stood out by generating an increase of 20%, whereas the other anthraquinones only produced a slight increase of 7%.

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Geranylated hydroquinones and other geranylated compounds isolated from Aplydium species have shown interesting biological activities. This fact has prompted a number of studies where geranylated phenol derivatives have been synthesized in order to assay their bioactivities. In this work, we report the synthesis of a series of new hydrated geranylphenols using two different synthetic approaches and their inhibitory effects on the mycelial growth of Botrytis cinerea. Five new hydrated geranylphenols were obtained by direct coupling reaction between geraniol and phenol in dioxane/water and using BF3·Et2O as the catalyst or by the reaction of a geranylated phenol with BF3·Et2O. Two new geranylated quinones were also obtained. The synthesis and structural elucidation of all new compounds is presented. All hydrated geranylphenols efficiently inhibit the mycelial growth of B. cinerea. Their activity is higher than that observed for non-hydrated compounds. These results indicate that structural modification on the geranyl chain brings about an enhancement of the inhibition effect of geranylated phenol derivatives.

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Gemifloxacin mesylate (GFM), chemically (R,S)-7-[(4Z)-3-(aminomethyl)-4-(methoxyimino)-1-pyrrolidinyl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid methanesulfonate, is a synthetic broad-spectrum antibacterial agent. Although many papers have been published in the literature describing the stability of fluorquinolones, little is known about the degradation products of GFM. Forced degradation studies of GFM were performed using radiation (UV-A), acid (1 mol L(-1) HCl) and alkaline conditions (0.2 mol L(-1) NaOH). The main degradation product, formed under alkaline conditions, was isolated using semi-preparative LC and structurally elucidated by nuclear magnetic resonance (proton - (1) H; carbon - (13) C; correlate spectroscopy - COSY; heteronuclear single quantum coherence - HSQC; heteronuclear multiple-bond correlation - HMBC; spectroscopy - infrared, atomic emission and mass spectrometry techniques). The degradation product isolated was characterized as sodium 7-amino-1-pyrrolidinyl-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate, which was formed by loss of the 3-(aminomethyl)-4-(methoxyimino)-1-pyrrolidinyl ring and formation of the sodium carboxylate. The structural characterization of the degradation product was very important to understand the degradation mechanism of the GFM under alkaline conditions. In addition, the results highlight the importance of appropriate protection against hydrolysis and UV radiation during the drug-development process, storage, handling and quality control.

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The search for anti-infective activity in the antipyretic plant Senecio smithioides was conducted. Petroleum ether (PE), dichloromethane (CH2Cl2), ethyl acetate (EtOAc) and hydroethanolic (96% EtOH) extracts, and compounds 9-oxoeuryopsin (1), epoxydecompostin (2) and senecionine (3) were obtained from the aerial parts. All extracts and 1 were tested against chloroquine-resistant strain of Plasmodium falciparum (ref. chloroquine), Trypanosoma cruzi (ref. nifurtimox), Leishmania braziliensis, Leishmania amazonensis and Leishmania donovani (ref. pentamidine), Staphylococcus aureus and Escherichia coli (ref. gentamicin) and, Neurospora crassa and Candida albicans (ref. ketoconazole). The PE extract exhibited the strongest in vitro activity against Plasmodium falciparum IC50 < 1.0 µg/mL. 1 was established as a potent antiplasmodial compound with an IC50 = 1.2 µg/mL, 5.2 µM. Other antiparasitic activities were recorded for all extracts and 1. Antibacterial and antifungal activity was negligible.