Sesquiterpenoids, alantolactone analogues, and seco-guaiene from the roots of Inula helenium

Three new sesquiterpenoids, a new unusual dimeric eudesmanolide, bialantolactone, a new nor-eudesmanolide, trinoralantolactone, and a new seco-guaiene, 7S,1(10)Z-4,5-seco-guaia-1(10),11-diene-4,5-dioxo, together with 13 known sesquiterpenoids, were isolated from the roots of Inula helenium. Their structures were elucidated by comprehensive spectroscopic analyses. The absolute configurations of bialantolactone and 7S,1(10)Z-4,5-seco-guaia-1(10),11-diene-4,5-dioxo were defined via the experimental and computational optical rotation and CD data. The plausible biosynthetic pathways to bialantolactone and 7S,1(10)Z-4,5-seco-guaia-1(10),11-diene-4,5-dioxo are discussed. 16 compounds were evaluated for their anti-bacterial activities against six bacteria.     

Isolation,Characterization, Complete Structural Assignment,and Anticancer Activities of the Methoxylated Flavonoids from Rhamnus disperma Roots

Different chromatographic methods including reversed-phase HPLC led to the isolation and purification of three O-methylated flavonoids; 5,4’-dihydroxy-3,6,7-tri-O-methyl flavone (penduletin) (1), 5,3’-dihydroxy-3,6,7,4’,5’-penta-O-methyl flavone (2), and 5-hydroxy-3,6,7,3’,4’,5’-hexa-O-methyl flavone (3) from Rhamnus disperma roots. Additionlly, four flavonoid glycosides; kampferol 7-O-α-L-rhamnopyranoside (4), isorhamnetin-3-O-β-D-glucopyranoside (5), quercetin 7-O-α-L-rhamnopyranoside (6), and kampferol 3, 7-di-O-α-L-rhamnopyranoside (7) along with benzyl-O-β-D-glucopyranoside (8) were successfully isolated. Complete structure characterization of these compounds was assigned based on NMR spectroscopic data, MS analyses, and comparison with the literature. The O-methyl protons and carbons of the three O-methylated flavonoids (1–3) were unambiguously assigned based on 2D NMR data. The occurrence of compounds 1, 4, 5, and 8 in Rhamnus disperma is was reported here for the first time. Compound 3 was acetylated at 5-OH position to give 5-O-acetyl-3,6,7,3’,4’,5’-hexa-O-methyl flavone (9). Compound 1 exhibited the highest cytotoxic activity against MCF 7, A2780, and HT29 cancer cell lines with IC₅₀ values at 2.17 µM, 0.53 µM, and 2.16 µM, respectively, and was 2–9 folds more selective against tested cancer cell lines compared to the normal human fetal lung fibroblasts (MRC5). It also doubled MCF 7 apoptotic populations and caused G₁ cell cycle arrest. The acetylated compound 9 exhibited cytotoxic activity against MCF 7 and HT29 cancer cell lines with IC₅₀ values at 2.19 µM and 3.18 µM, respectively, and was 6–8 folds more cytotoxic to tested cancer cell lines compared to the MRC5 cells.     

Synthesis of oryzalexins a,b and c,the diterpenoidal phytoalexins isolated from rice blast leaves infected with pyricularia oryzae

Naturally occurring enantiomers of three diterpenes isolated as phytoalexins from rice blast leaves were synthesized: (+)-oryzalexin.A [ent-3β-hydroxyisopimara-8(14),15-dien-7-one, 1], (+)-oryzalexin B [ent-7α-hydroxyisopimara-8(14),15-dien-3-one, 2] and (+)-oryzalexin C [ent-isopimara-8(14),15-diene-3,7-dione, 3]. Their antipodes were also synthesized.     

GC-MS,LC-MS/MS,Docking and Molecular Dynamics Approaches to Identify Potential SARS-CoV-2 3-Chymotrypsin-Like Protease Inhibitors from Zingiber officinale Roscoe

This study aims to identify and isolate the secondary metabolites of Zingiber officinale using GC-MS, preparative TLC, and LC-MS/MS methods, to evaluate the inhibitory potency on SARS-CoV-2 3 chymotrypsin-like protease enzyme, as well as to study the molecular interaction and stability by using docking and molecular dynamics simulations. GC-MS analysis suggested for the isolation of terpenoids compounds as major compounds on methanol extract of pseudostems and rhizomes. Isolation and LC-MS/MS analysis identified 5-hydro-7, 8, 2′-trimethoxyflavanone (9), (E)-hexadecyl-ferulate (1), isocyperol (2), N-isobutyl-(2E,4E)-octadecadienamide (3), and nootkatone (4) from the rhizome extract, as well as from the leaves extract with the absence of 9. Three known steroid compounds, i.e., spinasterone (7), spinasterol (8), and 24-methylcholesta-7-en-3β-on (6), were further identified from the pseudostem extract. Molecular docking showed that steroids compounds 7, 8, and 6 have lower predictive binding energies (MMGBSA) than other metabolites with binding energy of −87.91, −78.11, and −68.80 kcal/mole, respectively. Further characterization on the single isolated compound by NMR showed that 6 was identified and possessed 75% inhibitory activity on SARS-CoV-2 3CL protease enzyme that was slightly different with the positive control GC376 (77%). MD simulations showed the complex stability with compound 6 during 100 ns simulation time.     

Chemical Profile,Antioxidant Capacity,and Antimicrobial Activity of Essential Oils Extracted from Three Different Varieties (Moldoveanca 4, Vis Magic 10, and Alba 7) of Lavandula angustifolia

Chemical composition, antioxidant capacity, and antimicrobial activity of lavender essential oils (LEOs) extracted from three different varieties of Lavandula angustifolia Mill. (1-Moldoveanca 4, 2-Vis magic 10, and 3-Alba 7) have been determined. These plants previously patented in the Republic of Moldova were cultivated in an organic agriculture system in the northeastern part of Romania and then harvested in 3 consecutive years (2017–2019) to obtain the essential oils. From the inflorescences in the complete flowering stage, the LEOs were extracted by hydrodistillation. Then, their composition was analyzed by gas chromatography coupled with mass spectrometry (GC-MS) and by Fourier Transformed Infrared spectroscopy (FT-IR). The major identified constituents are as follows: linalool (1: 32.19–46.83%; 2: 29.93–30.97%; 3: 31.97–33.77%), linalyl acetate (1: 17.70–35.18%; 2: 27.55–37.13%; 3: 28.03–35.32%), and terpinen-4-ol (1: 3.63–7.70%; 2: 3.06–7.16%; 3: 3.10–6.53%). The antioxidant capacity as determined by ABTS and DPPH assays indicates inhibition, with the highest activity obtained for LEO var. Alba 7 from 2019. The in vitro antimicrobial activities of the LEOs and combinations were investigated as well, by using the disk diffusion method and minimum inhibitory concentration (MIC) against the Gram-positive bacterial strain Staphylococcus aureus (ATCC 6538), Gram-negative Pseudomonas aeruginosa (ATCC 27858), Escherichia coli (ATCC 25922), the yeast Candida albicans (ATCC 10231), and clinical isolates. Our results have shown that LEOs obtained from the three studied varieties of L. angustifolia manifest significant bactericidal effects against tested microorganisms (Staphylococcus aureus and Escherichia coli), and antifungal effects against Candida albicans. The mixture of LEOs (Var. Alba 7) and geranium, respectively, in tea tree EOs, in different ratios, showed a significant enhancement of the antibacterial effect against all the studied strains, except Pseudomonas aeruginosa.     

Preparation and structure of the light rare-earth copper selenides LnCuSe2 (Ln=La, Ce, Pr, Nd, Sm)

The ternary selenides LnCuSe₂ (Ln=La, Ce, Pr, Nd, Sm) have been synthesized by the reaction at 1173 K of Ln, Cu, and Se in a KBr or KI flux. The compounds, which are isostructural with LaCuS₂, crystallize with four formula units in the space group P2₁/c of the monoclinic system. The structure may be thought of as consisting of layers of CuSe₄ tetrahedra separated by double layers of LnSe₇ monocapped trigonal prisms along the a-axis. Cell constants (Å or deg) at 153 K are: LaCuSe₂, 6.8142(5), 7.5817(6), 7.2052(6), 97.573(1)°; CeCuSe₂, 6.7630(5), 7.5311(6), 7.1650(6), 97.392(1)°; PrCuSe₂, 6.740(1), 7.481(1), 7.141(1), 97.374(2)°; NdCuSe₂, 6.7149(6), 7.4452(7), 7.1192(6), 97.310(1)°; SmCuSe₂, 6.6655(6), 7.3825(7), 7.0724(6), 97.115(1)°. There are no Se-Se bonds in the structure of LnCuSe₂; the formal oxidation states of Ln/Cu/Se are 3+/1+/2−.     

Structure and magnetic properties of RE2CuIn3 (RE=Ce, Pr, Nd, Sm and Gd)

The ternary copper indides RE₂CuIn₃≡RECu_0.5In_1.5 (RE=Ce, Pr, Nd, Sm and Gd) were synthesized from the elements in sealed tantalum tubes in an induction furnace. They crystallize with the CaIn₂-type structure, space group P6₃/mmc, with a statistical occupancy of copper and indium on the tetrahedral substructure. These indides show homogeneity ranges RECu_xIn_2−x. Single crystal structure refinements were performed for five crystals: CeCu_0.66In_1.34 (a=479.90(7) pm, c=768.12(15) pm), PrCu_0.52In_1.48 (a=480.23(7) pm, c=759.23(15) pm), NdCu_0.53In_1.47 (a=477.51(7) pm, c=756.37(15) pm), SmCu_0.46In_1.54 (a=475.31(7) pm, c=744.77(15) pm), and GdCu_0.33In_1.67 (a=474.19(7), c=737.67(15) pm). Temperature-dependent susceptibility measurements show antiferromagnetic ordering at T_N=4.7 K for Pr₂CuIn₃ and Nd₂CuIn₃ and 15 K for Sm₂CuIn₃. Fitting of the susceptibility data of the samarium compound revealed an energy gap ΔE=39.7(7) K between the ground and the first excited levels.     

Crystal structures, magnetic and thermal properties of Ln3IrO7 (Ln=Pr, Nd, Sm, and Eu)

Ternary iridium oxides Ln₃IrO₇ (Ln=Pr, Nd, Sm, and Eu) were prepared and their crystal structures, magnetic and thermal properties were investigated. Powder X-ray diffractions (XRDs) were measured for all samples and neutron diffraction (ND) measurements were performed for Pr₃IrO₇. All the profiles were refined with space group Cmcm (No. 63). The lattice parameters for Pr₃IrO₇ refined by using ND data are a=10.9782(13) Å, b=7.4389(9) Å, and c=7.5361(9) Å. From specific heat and differential thermal analysis (DTA) measurements, Ln₃IrO₇ (Ln=Pr, Nd, Sm, and Eu) show thermal anomalies at 261, 342, 420, and 485 K, respectively. The results of powder high-temperature XRD and ND measurements indicate that these anomalies are due to the structural phase transition. Magnetic susceptibilities of these compounds were measured in the temperature range between 1.8 and 400 K. Nd₃IrO₇ shows an antiferromagnetic transition at 2.6 K. A specific heat anomaly has also been observed at the same temperature. For Ln₃IrO₇ (Ln=Pr, Sm, and Eu), no magnetic anomalies have been found in the experimental temperature range.     

Cadmium-Inspired Self-Polymerization of {LnIIICd2} Units: Structure,Magnetic and Photoluminescent Properties of Novel Trimethylacetate 1D-Polymers (Ln = Sm,Eu, Tb,Dy, Ho,Er, Yb)

A series of heterometallic carboxylate 1D polymers of the general formula [Ln^IIICd₂(piv)₇(H₂O)₂]_n·nMeCN (Ln^III = Sm (1), Eu (2), Tb (3), Dy (4), Ho (5), Er (6), Yb (7); piv = anion of trimethylacetic acid) was synthesized and structurally characterized. The use of Cd^II instead of Zn^II under similar synthetic conditions resulted in the formation of 1D polymers, in contrast to molecular trinuclear complexes with Ln^IIIZn₂ cores. All complexes 1–7 are isostructural. The luminescent emission and excitation spectra for 2–4 have been studied, the luminescence decay kinetics for 2 and 3 was measured. Magnetic properties of the complexes 3–5 and 7 have been studied; 4 and 7 exhibited the properties of field-induced single-molecule magnets in an applied external magnetic field. Magnetic properties of 4 and 7 were modelled using results of SA-CASSCF/SO-RASSI calculations and SINGLE_ANISO procedure. Based on the analysis of the magnetization relaxation and the results of ab initio calculations, it was found that relaxation in 4 predominantly occurred by the sum of the Raman and QTM mechanisms, and by the sum of the direct and Raman mechanisms in the case of 7.     

Serendipitous syntheses of the series Cs3Ln7Te12 (Ln = Sm,Gd, Tb): Compounds with large tunnels

Single crystals of Cs₃Ln₇Te₁₂ (Ln = Sm, Gd, Tb) have been grown accidentally through the reaction of Ln and Te with a CsCl or Cs₂Te₃ flux at elevated temperatures. The crystal structures have been determined from single crystal X-ray diffraction data. These compounds, which are isostructural with Rb₃Yb₇Se₁₂, crystallize in space group Pnnm of the orthorhombic system with two molecules in the following cells: Cs₃Sm₇Te₁₂, a=13.750(6), b=28.332(7), c=4.473(3) Å, T=293 K; Cs₃Gd₇Te₁₂, a=13.6064(13), b=28.209(3), c=4.4324(4) Å, T=153 K; Cs₃Tb₇Te₁₂, a=13.5708(16), b=28.116(3), c=4.4147(5) Å, T=153 K.     

Synthesis and photoluminescent properties of 7-N,N-diphenylamino-3- benzoheterocyclic coumarin derivatives

Two new 7-N,N-diphenylamino-3-benzoheterocyclic coumarin derivatives containing electron-transporting benzotriazolyl or benzoxazolyl moiety, 3-(1-benzotriazole)-7-N,N-diphenylaminocoumarin (BTDC) and 3-(2-benzoxazole)-7-N,N-diphenylaminocoumarin (BODC), were synthesized and characterized by element analysis, ¹H NMR and FT-IR spectra. The UV–vis and fluorescence spectra of these coumarin derivatives were investigated. The results show that BTDC and BODC exhibit strong blue and red emissions, respectively, under ultraviolet light excitation. The relationships between the chemical structure and the fluorescence characteristics of the 7-N,N-diphenylamino-3-benzoheterocyclic coumarin derivatives are discussed. It was found that the coumarin derivative will become a high-efficiency emitting material when an amino group is attached in 7-position of the coumarin ring, and 7- strong electron donors can improve the ability of the intramolecular charge transfer of the coumarin molecules.     

Determination of Pharmaceuticals,Heavy Metals,and Oxysterols in Fish Muscle

The present study aimed to assess the levels of 98 multi-class pharmaceuticals including cardiovascular drugs, antidepressants, hypnotics, antibiotics, and sulfonamides occurring in the muscle tissue of fish caught in the Baltic Sea. The following fish species were collected: perch (Perca fluviatilis); flounder (Platichthys flesus); turbot (Scophthalmus maximus); plaice (Pleuronectes platessa); cod (Gadus morhua callarias); bream (Abramis brama); crucian (Carassius carassius). Additionally, in the examined fish muscle the levels of heavy metals and trace elements were determined (As; Ag; Au; Ba; Cd; Co; Cr; Cu; Hg; Li; Mo; Ni; Pb; Sb; Se; Sn; Tl; V) as well as the levels of cholesterol and its 5 derivatives (7-ketocholesterol; 7α-hydroxycholesterol; 7β-hydroxycholesterol; 5β,6β-epoxy-cholesterol; 5α,6α-epoxycholesterol). In the performed studies 11 out of 98 examined pharmaceuticals were detected in fish muscle. The levels of pharmaceuticals in fish muscle varied depending on the species. In the tissues of bream and crucian, no pharmaceuticals were found. Mercury, lead and arsenic were detected in the muscles of all examined fish. Based on the hazard factor for Hg, Pb, Cd, Ni (target hazard quotient, THQ < 1), it was found that the consumption of the studied fish does not constitute a health risk. However, the THQ for As remained >1 indicated possible risk from those metals. In the examined fish muscle the total cholesterol oxidation products (COPs) level of oxysterols were, respectively: 6.90 (cod) μg/g–4.18 μg/g (perch), which corresponded to 0.7–1.5% of cholesterol. The main COPs evaluated were 7-ketocholesterol (0.78 ± 0.14–1.79 ± 0.06 μg/g), 7β-hydroxycholesterol (0.50 ± 0.04–3.20 ± 2.95 μg/g) and 5β,6β-epoxycholesterol (0.66 ± 0.03–1.53 ± 0.66 μg/g). The assessment of health hazards due to contaminations is necessary, which may help to introduce national legislation and global standards aimed at reducing or even eliminating the exposure to contaminants.     

Absolute configuration of (-)-biflora-4,10(19),15-triene,a diterpene from a termite soldier,as determined by the synthesis of its (1R, 6S, 7S, 11R)-(+)-isomer

(1R, 6S, 7S, 11R)-(+)-Biflora-4, 10(19),15-triene was synthesized starting from (r)-(+)-citronellic acid. This enabled us to assign (1S), 6R, 7R, (11S)-stereochemistry to the naturally occurring (-)-enantiomer isolated from soldiers of the termite species Cubitermes umbratus.     

The molecular structure of difluorophosphine selenide,determined using a combination of gas electron diffraction and liquid-crystal NMR data

The molecular structure of difluorophosphine selenide has been determined by a combined analysis of gas-phase electron diffraction data and dipolar couplings obtained for a solution in a nematic phase. Geometrical parameters (r_a) are: _r(PSe) 202.6(4), r(P-F) 155.7(3), r(P-H) 142.2(7) pm, ∠SePF 116.8(3), ∠FPF 98.1(7), ∠SePH 118.6(7)°.     

Cluster cations ejected from liquid metal ion source: alkali metals (Li,Na) and group IV elements (Si,Ge, Sn,Pb)

Cluster abundance of Li _n ⁺ (n≤19), Na _n ⁺ (n≤25), Si _n ^z+ (n≤8 forz=1, 3≤n≤7 forz=2), Ge _n ^z+ (n≤11 forz=1, 3≤n≤9 forz=2,n=4 forz=3), Sn _n ^z+ (n≤7 forz=1, 3≤n≤9 forz=2,n=4 forz=3) and Pb _n ^z+ (n≤6 forz=1, 5≤n≤7 forz=2) ejected from a liquid metal ion source has been investigated by mass spectrometry. The abundance spectra of alkali metal clusters showed distinct maxima and steps atn=3, 7, 9, 13 and 19 for Li, and atn=3, 5, 11, 13 and 19 for Na. Mass spectra of Si, Ge and Sn clusters were very similar each other, showing intensity drops aftern=4 and 6 (and alson=10 for Ge) for singly charged clusters. The magic numbers observed are discussed in terms of stability of charged clusters.     

Eremophilane,bakkane, secoeremophilane,and secobakkane sesquiterpenoids from Ligularia virgaurea collected in China

Secobakkane B (C-6/C-7 cleaved secobakkane type aldehyde), secovirgaurenols B and C (C-8/C-9 cleaved secoeremophilane type), a 1β,10β-epoxyfuranoeremophilane, two 1β,10β-epoxyeremophilanolides, and fukinospirolide C (bakkane-type lactone), as well as 33 known compounds were isolated from three samples of Ligularia virgaurea collected in China. Two of the three analyzed samples were grouped in the neoadenostylone (N) type, and the rest, a mixture of the 6-hydroxyeuryopsyn (H) and cacalol (C) types, out of five chemotypes found in this species.     

Thermodynamic dissociation constants of silychristin, silybin, silydianin and mycophenolate by the regression analysis of spectrophotometric data

Mixed dissociation constants of four drug acids, i.e. silychristin, silybinin, silydianin and mycophenolate at various ionic strengths I of range 0.01 and 0.30 and at temperatures of 25 and 37 °C were determined using the SQUAD(84) regression analysis program applied to pH-spectrophotometric titration data. The proposed strategy of an efficient experimentation in a protonation constants determination, followed by a computational strategy for the chemical model with a protonation constants determination, is presented on the protonation equilibria of silychristin. The thermodynamic dissociation constant pK_a^T was estimated by non-linear regression of {pK_a, I} data at 25 and 37 °C: for silychristin pK_a,1^T=6.52(16) and 6.62(1), pK_a,2^T=7.22(13) and 7.41(5), pK_a,3^T=8.96(9) and 8.94(9), pK_a,4^T=10.17(7) and 10.03(8), pK_a,5^T=11.89(4) and 11.63(7); for silybin pK_a,1^T=7.00(4) and 6.86(5), pK_a,2^T=8.77(11) and 8.77(3), pK_a,3^T=9.57(8) and 9.62(1), pK_a,4^T=11.66(3) and 11.38(1); for silydianin pK_a,1^T=6.64(7) and 7.10(6), pK_a,2^T=7.78(5) and 8.93(1), pK_a,3^T=9.66(9) and 10.06(11), pK_a,4^T=10.71(7) and 10.77(7), pK_a,5^T=12.26(5) and 12.14(5); for mycophenolate pK_a^T=8.32(1) and 8.14(1). Goodness-of-fit tests for various regression diagnostics enabled the reliability of parameter estimates to be found.     

Synthetic studies on nogalamycin congeners [3]1,2 total syntheses of (+)-nogarene, (+)-7-deoxynogarol,and (+)-7-con-o-methylnogarol

According to the retrosynthetic perspective, the title total syntheses were accomplished by employing the regioselective Diels-Alder reactions of the (+)-naphthoquinone (5), the CDEF-ring system of nogalamycin congeners, with various structural types of dienes (8, 16, and 26). The highly functionalized dienes (16 and 26) incorporating all the functionalities present in the A-rings of (+)-7-deoxynogarol (3) and (+)-7-con-O-methylnogarol (2), were prepared efficiently by way of the 1 ,4-cyclohexadiene and 2-cyclohexanone derivatives (6 and 21), respectively. Reaction mechanism of the key Diels-Alder reaction was also discussed in terms of its stereoselectivity.     

Oxandrastins: Antibacterial Meroterpenes from an Australian Mud Dauber Wasp Nest-Associated Fungus,Penicillium sp. CMB-MD14

The ethyl acetate extract of an ISP-2 agar cultivation of the wasp nest-associated fungus Penicillium sp. CMB-MD14 exhibited promising antibacterial activity against vancomycin-resistant enterococci (VRE), with a bioassay guided chemical investigation yielding the new meroterpene, oxandrastin A (1), the first andrastin-like metabolite with an extra oxygenation at C-2. A culture media optimisation strategy informed a scaled-up rice cultivation that yielded 1, together with three new oxandrastins B–D (2–4), two known andrastins C (5) and F (6), and a new meroterpene of the austalide family, isoaustalide F (7). Structures of 1–7 were assigned based on detailed spectroscopic analysis and chemical interconversion. A GNPS molecular networking analysis of the rice cultivation extract detected the known austalides B (8), H (9), and H acid (10), tentatively identified based on molecular formulae and co-clustering with 7. That the anti-VRE properties of the CMB-MD14 extract were exclusively attributed to 1 (IC₅₀ 6.0 µM, MIC₉₉ 13.9 µM), highlights the importance of the 2-OAc and 3-OAc moieties to the oxandrastin anti-VRE pharmacophore.