Search Results (20)

New technology has opened opportunities for research and exploration of deep-water ecosystems, highlighting deep-sea coral reefs as a rich source of novel bioactive natural products. During our ongoing investigation of the chemodiversity of the Irish deep sea and the soft coral Anthothela grandiflora, we report 12 unreported cadinene-like functionalized sesquiterpenes, anthoteibinenes F–Q. The metabolites were isolated using both bioassay- and ¹H NMR-guided approaches. One-/two-dimensional NMR spectroscopy and high-resolution mass spectrometry were used for structure elucidation, while a combination of NOESY NMR experiments, GIAO NMR calculations coupled with DP4+ probabilities measures, and ECD comparisons were incorporated to propose relative and absolute configurations of the anthoteibinenes. The metabolites were screened against the Respiratory Syncytial Virus (RSV), ESKAPE pathogens, five Candida albicans strains, and one strain of C. auris. Full article

The title compound was synthesized from perfluoro-1-ethyltetralin and 1,2,3,4-tetrafluorobenzene under the action of antimony pentafluoride as a mixture of cis- and trans-isomers in a 71% isolated yield. The structure and cis-/trans-configuration of the isomers were determined by NMR (¹⁹F, ¹³C), ¹⁹F–¹⁹F COSY, and ¹⁹F–¹⁹F NOESY 2D NMR spectroscopy. Full article

A study on the synergistic extraction of Eu(III) ions with a series of chelating ligands and determination of the process parameters is presented by employing ionic liquids and typical organic diluents. The investigations of the liquid–liquid extraction, commonly applied in the separation science of 4f and 5f-ions acidic chelating compounds, 4-benzoyl-3-methyl-1-phenyl-2-pyrazolin-5-one (HP), 4-benzoyl-3-phenyl-5-isoxazolone (HPBI), and 2-thenoyltrifluoroacetone (HTTA) alone and in combination with two synergistic agents, meso-hexamethylpropyleneamine oxime (S2: HM-PAO) and its bis-imine precursor (S1: pre-HM-PAO), are presented. The interaction between the two extractants (acidic/neutral) in deuterochloroform was studied using ¹H, ¹³C, and ¹H-¹H NOESY experiments. Several conclusions are given highlighting the role of the ionic diluent in complexation processes and selectivity with an employment of the two synergistic agents for various metal s-, p-, d-, and f-cations in the Periodic table, with almost 25 metal ions. The objective was to optimize a system for 4f-ions solvent extraction based on the new oxime molecules with β-diketone/isoxazolone/pyrazolone partnership. As detailed above, slight enhancements of extraction efficiencies were obtained either by using basic synergistic agents such as HM-PAO and/or using pre-HM-PAO. A competitive solvent extraction test of nearly 18 f-ions by various ligands (HTTA, S1, S2, and HPBI) and the two mixtures HTTA−S1 and HTTA−S2 diluted in ILs or organic diluents was also conducted in order to evaluate the switchable diluent impact. Additionally, electron paramagnetic resonance (EPR) spectroscopy was used to study the established chemical species with Cu²⁺ cations in the obtained organic extracts involving the two synergistic molecules. Full article

Two new aluminium hydrido complexes were synthesized by reacting AlH₃ with the enaminone ligand N-(4,4,4-trifluorobut-1-en-3-on)-6,6,6-trifluoroethylamine (HTFB-TFEA) in different molar ratios to obtain mono- and di-hydrido-aluminium enaminonates. Both air and moisture sensitive compounds could be purified via sublimation under reduced pressure. The spectroscopic analysis and structural motif of the monohydrido compound [H-Al(TFB-TBA)₂] (3) showed a monomeric 5-coordinated Al(III) centre bearing two chelating enaminone units and a terminal hydride ligand. However, the dihydrido compound exhibited a rapid C-H bond activation and C-C bond formation in the resulting compound [(Al-TFB-TBA)-HCH2] (4a), which was confirmed by single crystal structural data. The intramolecular hydride shift involving the migration of a hydride ligand from aluminium centre to the alkenyl carbon of the enaminone ligand was probed and verified by multi-nuclear spectral studies (¹H,¹H NOESY, 13C, ¹⁹F, and ²⁷Al NMR). Full article

The understanding of the mechanism of Topo I inhibition by organic ligands is a crucial source of information that has led to the design of more effective and safe pharmaceuticals in oncological chemotherapy. The vast number of inhibitors that have been studied in this respect over the last decades have enabled the creation of a concept of an ‘interfacial inhibitor’, thereby describing the machinery of Topo I inhibition. The central module of action of this machinery is the interface of a Topo I/DNA/inhibitor ternary complex. Most of the ‘interfacial inhibitors’ are primarily kinetic inhibitors that form molecular complexes with an “on–off” rate timing; therefore, all of the contacts between the inhibitor and both the enzyme and the DNA are essential to keep the complex stable and reduce the “off rate”. To test this hypothesis, we designed the compound using a C-9-(N-(2′-hydroxyethyl)amino)methyl substituent in an SN38 core, with a view that a flexible substituent may bind inside the nick of a model of the DNA and stabilize the complex, leading to a reduction in the “off rate” of a ligand in a potential ternary complex in vivo. Using docking analysis and molecular dynamics, free energy calculations on the level of the MM-PBSA and MM-GBSA model, here we presented the in silico-calculated structure of a ternary complex involving the studied compound 1. This confirmed our suggestion that compound 1 is situated in a groove of the nicked DNA model in a few conformations. The number of hydrogen bonds between the components of a ternary complex was established, which strengthens the complex and supports our view. The docking analysis and free energy calculations for the receptor structures which were obtained in the MD simulations of the ternary complex 1/DNA/Topo I show that the binding constant is stronger than it was for similar complexes with TPT, CPT, and SN38, which are commonly considered as strong Topo I inhibitors. The binary complex structure 1/DNA was calculated and compared with the experimental results of a complex that was in a solution. The analysis of the cross-peaks in NOESY spectra allowed us to assign the dipolar interactions between the given protons in the calculated structures. A DOSY experiment in the solution confirmed the strong binding of a ligand in a binary complex, having a K_a of 746 mM⁻¹, which was compared with a K_a of 3.78 mM⁻¹ for TPT. The MALDI-ToF MS showed the presence of the biohybrid, thus evidencing the occurrence of DNA alkylation by compound 1. Because of it having a strong molecular complex, alkylation is the most efficient way to reduce the “on–off” timing as it acts as a tool that causes the cog to brake in a working gear, and this is this activity we want to highlight in our contribution. Finally, the Topo I inhibition test showed a lower IC₅₀ of the studied compound than it did for CPT and SN38. Full article

Laying the groundwork on preliminary structure–activity relationship study relating to the disruptive activity of cytochalasan derivatives on mammalian cell actin cytoskeleton, we furthered our study on the cytochalasans of the Dothideomycetes fungus, Sparticola triseptata. A new cytochalasan analog triseptatin (1), along with the previously described cytochalasans deoxaphomin B (2) and cytochalasin B (3), and polyketide derivatives cis-4-hydroxy-6-deoxyscytalone (4) and 6-hydroxymellein (5) were isolated from the rice culture of S. triseptata. The structure of 1 was elucidated through NMR spectroscopic analysis and high-resolution mass spectrometry (HR-ESI-MS). The relative and absolute configurations were established through analysis of NOESY spectroscopic data and later correlated with experimental electronic circular dichroism and time-dependent density functional theory (ECD–TDDFT) computational analysis. Compounds 1 and 2 showed cytotoxic activities against seven mammalian cell lines (L929, KB3.1, MCF-7, A549, PC-3, SKOV-3, and A431) and antiproliferative effects against the myeloid leukemia K-562 cancer cell line. Both 1 and 2 were shown to possess properties inhibiting the F-actin network, prompting further hypotheses that should to be tested in the future to enable a well-resolved concept of the structural implications determining the bioactivity of the cytochalasin backbone against F-actin. Full article

Herein, we report a facile synthesis of ethyl-2-(4-aminophenoxy)acetate 4 as a building synthon for novel dual hypoglycemic agents. This building template was synthesized by alkylation of 4-nitrophenol with ethyl bromo-acetate followed by selective reduction of the nitro group. This reduction methoddoes not require nascent hydrogen or any reaction complexity; it goes easily via consecutive reaction in NH₄Cl/Fe to yield our target synthon as very pure crystals. This product was characterized by ¹HNMR, ¹³CNMR, COSY, NOESY NMR spectroscopy, and elemental analysis. Additionally, its structure was studied and approved by X-ray single crystal structure determination. The unit cell parameters are a = 8.2104(6)Å, b = 10.3625(9)Å, c = 11.9562(9)Å, α = 101.787(7), β = 91.849(6), and γ = 102.755(7)°, indicating that 4 was crystallized in the triclinic crystal system. The cooperative non-covalent interactions are also discussed with the aid of Hirshfeld surface analysis. The H…H, H…C, and O…H interactions have a major contribution in the molecular packing of 4. Moreover, different quantum chemical parameters were computed and discussed based on DFT calculations. The experimental UV/Vis spectra showed two bands at 299 and 234 nm, which were calculated using the TD-DFT method at 286 (f = 0.068) and 226 nm (f = 0.294), respectively. These bands were assigned to HOMO→LUMO (95%) and HOMO→LUMO+2 (86%) transitions, respectively. Full article

Application of LC-MS/MS-based molecular networking indicated the ethanol extract of octocoral Asterospicularia laurae is a potential source for the discovery of new xenicane derivatives. A natural product investigation of this soft coral resulted in the isolation of four new xenicane diterpenoids, asterolaurins O–R (1–4), together with six known compounds, xeniolide-A (5), isoxeniolide-A (6), xeniolide-B (7), 7,8-epoxyxeniolide-B (8), 7,8-oxido-isoxeniolide-A (9), and 9-hydroxyxeniolide-F (10). The structures of isolated compounds were characterized by employing spectroscopic analyses, including 2D-NMR (COSY, HMQC, HMBC, and NOESY) and high-resolution electrospray ionization mass spectrometry (HRESIMS). Asterolaurin O is the first case of brominated tricarbocyclic type floridicin in the family Xeniidae. Concerning bioactivity, the cytotoxic activity of those isolates was evaluated. As a result, compounds 1 and 2 demonstrated a selective cytotoxic effect against the MCF-7 cell line at IC₅₀ of 14.7 and 25.1 μM, respectively. Full article

The present investigation on chemical constituents of the soft coral Sarcophyton cherbonnieri resulted in the isolation of seven new cembranoids, cherbonolides F–L (1–7). The chemical structures of 1–7 were determined by spectroscopic methods, including infrared, one- and two-dimensional (1D and 2D) NMR (COSY, HSQC, HMBC, and NOESY), MS experiments, and a chemical reduction of hydroperoxide by triphenylphosphine. The anti-inflammatory activities of 1–7 against neutrophil proinflammatory responses were evaluated by measuring their inhibitory ability toward N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLF/CB)-induced superoxide anion generation and elastase release in primary human neutrophils. The results showed that all isolates exhibited moderate activities, while cherbonolide G (2) and cherbonolide H (3) displayed a more active effect than others on the inhibition of elastase release (48.2% ± 6.2%) and superoxide anion generation (44.5% ± 4.6%) at 30 µM, respectively. Full article

A series of iridoid glycosides were isolated from the leaves of Lasianthus verticillatus (Lour.) Merr., belonging to family Rubiaceae. A new iridoid glycoside, lasianoside F (1), and three new bis-iridoid glycosides, lasianosides G–I (2–4), together with four known compounds (5–8) were isolated. The structures were established by spectroscopic methods, including 1D and 2D NMR experiments (¹H, ¹³C, DEPT, COSY, HSQC, HMBC, and NOESY) in combination with HR-ESI-MS and CD spectra. Full article

Genus Stachys, the largest genera of the family Lamiaceae, and its species are frequently used as herbal teas due to their essential oils. Tubers of some Stachys species are also consumed as important nutrients for humans and animals due to their carbohydrate contents. Three new neo-clerodane diterpene peroxides, named stachaegyptin F-H (1, 2, and 4), together with two known compounds, stachysperoxide (3) and stachaegyptin A (5), were isolated from Stachys aegyptiaca aerial parts. Their structures were determined using a combination of spectroscopic techniques, including HR-FAB-MS and extensive 1D and 2D NMR (¹H, ¹³C NMR, DEPT, ¹H-¹H COSY, HMQC, HMBC and NOESY) analyses. Additionally, a biosynthetic pathway for the isolated compounds (1–5) was discussed. The chemotaxonomic significance of the isolated diterpenoids of S. aegyptiaca in comparison to the previous reported ones from other Stachys species was also studied. Full article

Six new carotane sesquiterpenoids piltunines A–F (1–6) together with known compounds (7–9) were isolated from the marine-derived fungus Penicillium piltunense KMM 4668. Their structures were established using spectroscopic methods. The absolute configurations of 1–7 were determined based on circular dichroism (CD) and nuclear Overhauser spectroscopy (NOESY) data as well as biogenetic considerations. The cytotoxic activity of some of the isolated compounds and their effects on regulation of reactive oxygen species (ROS) and nitric oxide (NO) production in lipopolysaccharide-stimulated macrophages were examined. Full article

Four new structurally related metabolites, one γ-lactone named gliomasolide F (1), one δ-lactone named gliomasolide G (2), and two medium-chain fatty acids named gliomacids A–B (3–4), each containing nine carbons in total, were identified from the sponge-associated fungus Gliomastix sp. ZSDS1-F7-2. The planar chemical structures of these novel C9 metabolites were elucidated by nuclear magnetic resonance (NMR) spectroscopic methods, in connection with the analysis of high-resolution mass spectrometry (HRMS) and infrared (IR) data. The absolute configuration of 1, was determined by comparisons of experimental circular dichroism (CD) and optical rotation (OR) value with corresponding ones computed by quantum chemistry. The relative configuration of 2 was determined by the Nuclear Overhauser effect spectroscopy (NOESY) spectrum, while its absolute configuration was tentatively determined in view of the biogenetic and biosynthetic relationships between 1 and 2. Compounds 3–4, originally as an inseparable mixture, were successfully isolated after chemical modifications. The stereo-chemistries of compounds 3–4 were assumed by comparison of ¹³C NMR with those of the similar moiety reported in literature, in addition to the biogenetic and biosynthetic relationships with 1. The plausible biosynthetic relationships among these four C9 metabolites were supposed. Biologically, compounds 1–4 showed no cytotoxic effect against HeLa cell line at concentrations up to 25 μg/mL, while 1 exhibited moderate antifouling activity against the settlement of Balanus amphitrite larvae with IC₅₀ being 12.8 μg/mL and LC₅₀ > 25 μg/mL. The co-occurrence of macrolides gliomasolides A—E and four C9 metabolites in the same fermentation culture made us assume that these C9 metabolites might be biosynthetic building blocks toward the construction of more complex macrolides such as gliomasolides A—E or other unidentified polyketides. Full article

In the last 20 years, a huge volume of experimental work into halogen bonding (XB) has been produced. Most of the systems have been characterized by solid state X-ray crystallography, whereas in solution the only routine technique is titration (by using ¹H and ¹⁹F nuclear magnetic resonance (NMR), infrared (IR), ultraviolet–visible (UV–Vis) or Raman spectroscopies, depending on the nature of the system), with the aim of characterizing the strength of the XB interaction. Unfortunately, titration techniques have many intrinsic limitations and they should be coupled with other, more sophisticated techniques to provide an accurate and detailed description of the geometry and stoichiometry of the XB adduct in solution. This review will show how crucial information about XB adducts can be obtained by advanced NMR techniques, nuclear Overhauser effect-based spectroscopies (NOESY, ROESY, HOESY…) and diffusion NMR techniques (PGSE or DOSY). Full article