Comprehensive 2D Research Articles

Dobutamine stress echocardiography unmasks early left ventricular dysfunction in asymptomatic patients with uncomplicated Type 2 diabetes: A comprehensive 2D speckle-tracking imaging Study

Discrepancies are present in the literature on resting myocardial mechanics in patients with uncomplicated type 2 diabetes mellitus (T2DM). Data are noticeably sparse regarding circumferential function and torsional mechanics. Resting deformation imaging may not be sensitive enough to detect subtle dysfunctions. The aim of this study was thus to comprehensively evaluate myocardial mechanics in patients with T2DM at rest and to investigate whether dobutamine stress echocardiography could unmask functional alterations that would remain otherwise subtle at rest. Forty-four patients with T2DM and 35 healthy control subjects of similar age and sex were prospectively recruited. After conventional echocardiography, myocardial mechanics was evaluated at rest and during low-dose dobutamine stress echocardiography (target heart rate, 110 beats/min). Patients with T2DM presented with altered global diastolic function but preserved systolic function. Deformation imaging indexes were similar between groups at rest, but significant differences were noticed under dobutamine infusion ( Table 1 ). Multivariate analysis identified epicardial fat, dyslipidemia, and fasting glycaemia as significant contributors to the changes from rest to dobutamine. These findings demonstrate the usefulness of dobutamine stress echocardiography in establishing impairments in myocardial mechanics in patients with uncomplicated T2DM. Systemic metabolic disturbances and epicardial fat act as the main contributors to the blunted response to dobutamine stress in these patients.

Comprehensive Phenotypic Characterization of Human Invasive Lobular Carcinoma Cell Lines in 2D and 3D Cultures.

Invasive lobular carcinoma (ILC) is the second most common subtype of breast cancer following invasive ductal carcinoma (IDC) and characterized by the loss of E-cadherin-mediated adherens junctions. Despite displaying unique histologic and clinical features, ILC still remains a chronically understudied disease, with limited knowledge gleaned from available laboratory research models. Here we report a comprehensive 2D and 3D phenotypic characterization of four estrogen receptor-positive human ILC cell lines: MDA-MB-134, SUM44, MDA-MB-330, and BCK4. Compared with the IDC cell lines MCF7, T47D, and MDA-MB-231, ultra-low attachment culture conditions revealed remarkable anchorage independence unique to ILC cells, a feature not evident in soft-agar gels. Three-dimensional Collagen I and Matrigel culture indicated a generally loose morphology for ILC cell lines, which exhibited differing preferences for adhesion to extracellular matrix proteins in 2D. Furthermore, ILC cells were limited in their ability to migrate and invade in wound-scratch and transwell assays, with the exception of haptotaxis to Collagen I. Transcriptional comparison of these cell lines confirmed the decreased cell proliferation and E-cadherin-mediated intercellular junctions in ILC while uncovering the induction of novel pathways related to cyclic nucleotide phosphodiesterase activity, ion channels, drug metabolism, and alternative cell adhesion molecules such as N-cadherin, some of which were differentially regulated in ILC versus IDC tumors. Altogether, these studies provide an invaluable resource for the breast cancer research community and facilitate further functional discoveries toward understanding ILC, identifying novel drug targets, and ultimately improving the outcome of patients with ILC.Significance: These findings provide the breast cancer research community with a comprehensive assessment of human invasive lobular carcinoma (ILC) cell line signaling and behavior in various culture conditions, aiding future endeavors to develop therapies and to ultimately improve survival in patients with ILC. Cancer Res; 78(21); 6209-22. ©2018 AACR.

A Novel Online Four-Dimensional SEC×SEC-IM×MS Methodology for Characterization of Monoclonal Antibody Size Variants.

The determination of size variants is a major critical quality attribute of a therapeutic monoclonal antibody (mAb that may affect the drug product safety, potency, and efficacy. Size variant characterization often relies on size-exclusion chromatography (SEC), which could be hampered by difficult identification of peaks. On the other hand, mass spectrometry (MS)-based techniques performed in nondenaturing conditions have proven to be valuable for mAb-related compound characterization. On the basis of the observation that limited SEC performance was observed in nondenaturing MS compatible ammonium acetate buffer compared with classical phosphate salts, a multidimensional analytical approach was proposed. It combines comprehensive online two-dimensional chromatography (SEC×SEC), with ion mobility and mass spectrometry (IM-MS) in nondenaturing conditions for the characterization of a variety of mAbs. We first exemplify the versatility of our approach for simultaneous detection, identification, and quantitation of adalimumab size variants. Benefits of the SEC×SEC-native IM×MS were further highlighted on forced degraded pembrolizumab and bevacizumab samples, for which the 4D setup was mandatory to obtain an extensive and unambiguous identification, and accurate quantitation of unexpected high/low molecular weight species (HMWS and LMWS). In this specific context, monomeric conformers were detected by IM-MS as HMWS or LMWS. Altogether, our results emphasize the power of comprehensive 2D LC×LC setups hyphenated to IM×MS in nondenaturing conditions with unprecedented performance including: (i) maintaining optimal SEC performance (under classical nonvolatile salt conditions), (ii) performing online native MS identification, and (iii) providing IM-MS conformational characterization of all separated size variants.

Antileishmanial Carbasugars from Geosmithia langdonii.

Two new carbasugar-type metabolites, (1 S,2 R,3 R,4 R,5 R)-2,3,4-trihydroxy-5-methylcyclohexyl-2',5'-dihydroxybenzoate (1) and (1 S,2 S,3 S,4 R,5 R)-4-[(2',5'-dihydroxybenzyl)oxy]-5-methylcyclohexane-1,2,3-triol (2), were isolated from the filamentous fungus Geosmithia langdonii isolated from cotton textiles from Assiut, Egypt. The structures of 1 and 2 were elucidated based on comprehensive 1D and 2D NMR and MS data. Compounds 1 and 2 showed antileishmanial activity against Leishmania donovani with IC50 values of 100 and 57 μM, respectively. The (1 S,2 R,3 R,4 R,5 R) absolute configuration of carbasugar 1 was assigned via 2D NMR and experimental and calculated electronic circular dichroism (ECD) data. Similarly, the tentative structure of compound 2 was shown to possess a (1 S,2 S,3 S,4 R,5 R) absolute configuration via comparing its experimental ECD data and the specific rotation with 1 as well as examining the energy-minimized 3D computational models of compounds 1 and 2.

Two-Dimensional Biochemical Purification for Global Proteomic Analysis of Macromolecular Protein Complexes.

A high-resolution two-dimensional (2-D) proteomic fractionation technique for the systematic purification and subsequent mass spectrometry-based identification of endogenous protein macromolecular complexes is described. The method hyphenates preparative isoelectric focusing (IEF) with mixed-bed ion exchange chromatography (IEX) to efficiently separate cell- or tissue- derived soluble protein mixtures, allowing for more effective and less biased physiochemical characterization of stable multiprotein assemblies. After comprehensive 2D fractionation of cell-free lysates, each fraction is subjected to quantitative tandem mass spectrometry (MS/MS) and subsequent computational analysis to map high-confidence protein-protein interactions (PPIs). Herein, the experimental component (workflow protocols) for this global "interactome" network mapping platform is described.

Intraoperative 3-Dimensional Echocardiography–Derived Right Ventricular Volumetric Analysis in Chronic Thromboembolic Pulmonary Hypertension Patients Before and After Pulmonary Thromboendarterectomy

To assess the change in 3-dimensional (3D) echocardiography-derived right ventricular volumes before and after pulmonary thromboendarterectomy (PTE) and to evaluate the correlation of these variables with right heart catheterization-calculated pulmonary vascular resistance (PVR). Single university hospitals. Patients undergoing elective PTE surgery between November 2016 and February 2018. All patients received a pulmonary artery catheter and arterial line, and transesophageal echocardiographic monitoring was performed. Transesophageal echocardiographic monitoring before surgery (pre-PTE) and postsurgery (post-PTE) included comprehensive 2D examinations and 3D right ventricular data set acquisition for offline volumetric analysis. Right ventricular fractional area of change (RVFAC) was measured from a right ventricular-focused midesophageal 4-chamber view. TomTec-Arena 4D RV-Function 2.0 offline software (TomTec Imaging Systems GmbH, Unterschlessheim, Germany) was used to measure right ventricular end diastolic volume (RVEDV), right ventricular end systolic volume (RVESV), and right ventricular ejection fraction (RVEF). Paired t tests were used to evaluate for differences before and after surgery, and echocardiographic variables versus PVR were analyzed with linear regression. Forty patients were scheduled for elective PTE surgery; 35 patients had complete hemodynamic profiles and echocardiographic data sets and were included in the evaluation. Mean pulmonary artery pressure decreased from 40 ± 11 to 28 ± 7 mmHg, and PVR decreased from 708 ± 432 to 285 ± 136 dynes*s/cm5 after PTE. RVEDV decreased from 106 ± 43 to 79 ± 35 cm3 (p < 0.001), and RVESV decreased from 77 ± 36 to 59 ± 31 cm3 (p < 0.001). A statistically significant change was not identified in RVEF or RVFAC post-PTE compared with pre-PTE values. All volumetric analyses and RVFAC correlated poorly with PVR (pre-PTE RVEDV correlation to PVR [R2 = 0.004]; post-PTE RVEDV correlation to PVR [R2 = 0.024]). Even though RVEDV and RVESV displayed a statistically significant change after PTE, this study did not identify a correlation between those variables and PVR. In addition, markers of right ventricular systolic function (eg, RVFAC and RVEF) did not correlate with PVR. Therefore, the authors conclude that even though these echocardiographic measurements quantified a statistically significant change after PVR reduction, they cannot be reliably used as a surrogate marker of success immediately after PTE.

TSR, deep oil cracking and exploration potential in the Hetianhe gas field, Tarim Basin, China

Oil and gas in deep and ultra-deep strata has been a hot topic in both research and exploration. The understanding of reservoirs in relatively shallow strata may be of significance for deep exploration. The Hetianhe gas field is the only large gas field discovered yet in the southwest region of the Tarim Basin, with a small quantity of condensate oil penetrated and a burial depth ranging from 1035 m to 2885 m, and the origin and source of the oil and gas has long been unclear. By using comprehensive 2D gas chromatography/time of flight mass spectrometry (GC × GC-TOFMS), abundant diamondoids and some thiadiamondoids were detected in condensate oil samples collected from 3 wells, additionally, the features, including dry gas with a trace amount of hydrogen sulfide, heavy carbon isotopes, and similar sulfur isotopes in hydrogen sulfide and Cambrian gypsum, indicate that the oil and gas has undergone the thermochemical sulfate reduction (TSR) and thermal cracking. The current reservoir temperature, from 35 °C to 83 °C, does not meet the condition for the onset of these secondary geochemical alterations, therefore, the oil and gas may originate from deep strata. According to the reconstruction of the geologic evolution, deep oil and gas may have migrated vertically along faults and accumulated in the Hetianhe structure formed after 10 Ma to form the secondary gas reservoirs; hence it is inferred that favorable petroleum plays may exist in deep strata. The thick evaporite in the Middle Cambrian and the high-quality dolomite reservoirs in the Lower Cambrian constitute a favorable reservoir-seal assemblage, with the current depth between 8500 m and 10000 m and reservoir temperature above 200 °C, where the TSR and thermal cracking may occur. The sulfur isotope of hydrogen sulfide also demonstrates the occurrence of TSR process in the Cambrian strata. Therefore, large-scale of oil and gas reserves may be preserved in the stable zones in the Cambrian sub-salt strata, and it is suggested to strengthen hydrocarbon exploration in the Cambrian sub-salt strata in the southwest region of the Tarim Basin.

Two new bioactive steroids from a mangrove-derived fungus Aspergillus sp.

Two unusual naturally Diels-Alder additive steroids, ergosterdiacids A and B (1 and 2), constructing a 6/6/6/6/5 pentacyclic steroidal system, together with three known compounds (3–5) were obtained from the mangrove-derived fungus Aspergillus sp. Their structures were elucidated based on the comprehensive spectroscopic analysis, including 1D, 2D NMR and HRESIMS, as well as the quantum chemical ECD calculations. The plausible biosynthetic pathways of 1 and 2 were discussed. In the bioactivity assays, 1 and 2 exhibited potential in vitro inhibition activity against Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) with an IC50 value of 15.1 and 30.1 μM, respectively. The inhibitory kinetic experiments indicated that both of them acted via a noncompetitive inhibition mechanism. Moreover, 1 and 2 showed strong in vitro anti-inflammatory effects by suppressing the NO production at 4.5 and 3.6 μM, respectively.

Correlation between Comprehensive 2D Liquid Chromatography and Monte Carlo Simulations for Branched Polymers

Detailed knowledge on structural information is required to derive the rheological properties of branched polymers. Size-exclusion chromatography with triple-detection (TD-SEC), comprising a concentration, a light scattering, and a viscosity detector, is a powerful tool to analyze the degree of branching of polymers as a function of their molar masses. However, TD-SEC alone is incapable of fully deconvoluting complex polymer systems. In this study we discuss a more sophisticated approach that includes coupling of TD to our recently described novel online two-dimensional liquid chromatography method (2D-LC), based on solvent gradient at near-critical conditions in the first dimension. Thus, a contour plot of the branching ratio is presented, and unique detailed information on the degree of branching can be derived for branched polycarbonate (PC) sample. Furthermore, the molar mass distributions of separated linear and branched PC chains as well as their fractions in the polymer are quantified. The correspo...

Separation and identification of polymeric dispersants in detergents by two-dimensional liquid chromatography

Polymeric dispersants are an important ingredient in many consumer products. Their separations and identifications in final product formulation can be very challenging due to the presence of multiple polymeric dispersants at different levels and the presence of other polymeric and small-molecule components. In this study, using nearly comprehensive two-dimensional liquid chromatography (2D-LC), various water-soluble polymer and co-polymer dispersants were separated with aqueous size exclusion chromatography (SEC) in the first dimension (1D) and gradient elution reversed-phase liquid chromatography (RPLC) in the second dimension (2D). Detection of the polymeric dispersants was accomplished by evaporative light scattering detector (ELSD). A large ID (8.0 mm) SEC column used in common one-dimensional SEC practices was directly adopted in the 2D setup for rapid method development. A close representation of fully comprehensive 2D separation was achieved even with 60% of 1D eluent diverted to waste, demonstrating the flexibility and versatility of having SEC in 1D for two dimensional separation of polymers. Important method parameters, such as 2D column dimensions and flow rate, gradient conditions, and buffer pH were studied. Practical aspects of routine industrial applications such as solvent consumption and analysis time were also considered. This method was exploited for quick identification of polymeric dispersants in commercial detergent samples. Nine detergent samples were screened and polymeric dispersants and additional polymer features were detected in the samples.

A new feruloyl glyceride from the roots of Asian rice (Oryza sativa)

Oryza sativa L., Poaceae, is the most important staple food in the world and provides food for more than half of the world's population. The roots of O. sativa have been used as a traditional medicine in Korea. As part of our continuing efforts to explore structurally new compounds from Korean natural resources, two feruloyl glycerides, 2-O-(E)-feruloyl glyceride (1) and 2-O-(Z)-feruloyl glyceride (2), which is a new compound, together with one known flavonoid, 8-hydroxyacacetin (3), were isolated from the ethanolic extract of the roots of O. sativa using an LC/MS-guided isolation method. The chemical structure of compound 2 was elucidated based on comprehensive 1D and 2D NMR spectroscopic experiments and HR-ESIMS. This study represents the first report of feruloyl glycerides (1–2) identified in O. sativa. In addition, the identification of compound 3 is reported from Asian rice (O. sativa) for the first time. The cytotoxic activities of the isolates 1–3 were evaluated by determining their inhibitory effects on A2780 human ovarian carcinoma cells.

Combination of comprehensive two-dimensional prostate cancer cell membrane chromatographic system and network pharmacology for characterizing membrane binding active components from Radix et Rhizoma Rhei and their targets

Prostate cancer (PCa) is a common and fatal cancer for men and effective treatment options are still not enough for patients. Radix et Rhizoma Rhei had been applied to treat PCa long-termly and effectively when combined with surgical treatment and chemotherapy. However, its active components and target proteins are still not quite clear. As membrane receptors play a vital role in PCa, in this study, a novel strategy that combines comprehensive 2D 3-aminopropyltriethoxysilane-decorated prostate cancer cell (DU145) membrane chromatographic (CMC) system with network pharmacology approach was developed to characterize membrane binding active components proteins from Radix et Rhizoma Rhei and their targets. Thirteen active components were screened out by CMC system, among which emodin and rhapontigrnin with good membrane binding behaviors were validated to show ideal inhibitory effects on DU145 cells by cell viability and cell apoptosis assays. Five membrane proteins were predicted as the potential targets by the a specific network pharmacology approach, among which mast/stem cell growth factor receptor Kit (KIT) was identified as the most possible target by network data mining. Surface plasmon resonance analysis verified that the dissociation constant (KD) of rhapontigrnin and emodin with KIT was 6.06 × 10−5 M and 8.82 × 10−5 M, respectively. Our results showed that the combination of comprehensive 2D CMC system and network pharmacology based target identification could not only rapidly identify the membrane binding components but also find the potential membrane protein targets with high confidence, which could broaden the range of application scope of CMC, especially for the screening of active compounds from complex chemical samples using primary pathologic cell lines.

Nitrogenous Compounds Produced by the Deep Sea Derived Fungus Leptosphaeria sp. SCSIO 41005

Four nitrogenous compounds, including two new compounds methyl-4-((1-hydroxy-3-methylpentan-2-yl)amino)–3-methyl-4-oxobutanoate (1), 4-((1-acetoxy-3-methylpentan-2-yl)amino)–3-methyl-4-oxobutanoic acid (2), and two amino acid derivatives (3, 4), were isolated from the deep sea derived fungus Leptosphaeria sp. SCSIO 41005, together with a cyclohexanone derivative (5) as new natural compound and other three known compounds (6–8). Their structures were elucidated by means of comprehensive 1D, 2D NMR and HR-ESI-MS spectroscopic methods. All the compounds were evaluated for their cytotoxic and antiviral activities.

Mapping and quantifying isomer sets of hydrocarbons ( ≥ C12) in diesel exhaust, lubricating oil and diesel fuel samples using GC × GC-ToF-MS

Abstract. Airborne particles and vapours, like many other environmental samples including water, soils and sediments, contain complex mixtures of hydrocarbons, often deriving from crude oil either before or after fractionation into fuels, lubricants and feedstocks. Comprehensive 2D gas chromatography time-of-flight mass spectrometry (GC × GC-ToF-MS), offers a very powerful technique that separates and identifies many compounds in complicated hydrocarbon mixtures. However, quantification and identification of individual constituents at high ionization energies would require hundreds of expensive (when available) standards for calibration. Although the precise chemical structure of hydrocarbons does matter for their environmental impact and fate, strong similarities can be expected for compounds having very similar chemical structures and carbon numbers. There is, therefore, a clear benefit in an analytical technique which is specific enough to separate different classes of compounds and to distinguish homologous series while avoiding the need to handle each isomer individually. Varying EI (electron impact) ionization mass spectrometry significantly enhances the identification of individual isomers and homologous compound groups, which we refer to as “isomer sets”. Advances are reported in mapping and quantifying isomer sets of hydrocarbons (≥ C12) in diesel fuel, lubricating oil and diesel exhaust emissions. By using this analysis we report mass closures of ca. 90 and 75 % for diesel fuel and lubricating oil, and identify 85 and 75 % of the total ion current for gas- and particulate-phase diesel exhaust emissions.

A new labdane-type diterpenoid from Leonurus japonicus

Five fractions prepared from the crude extract of Leonurus japonicus were examined in order to determine their cytotoxic potential. Under the bioassay guidance, a new labdane-type diterpenoid (1), and nine known ones (2–10) along with a seco-labdane (11) were isolated from the aerial parts of Leonurus japonicus. The structure elucidation was primarily based on comprehensive spectroscopic analyses, including HRESIMS, IR, and 1D and 2D NMR methods. Compound 4 (6β-hydroxy-15,16-epoxylabda-8,13(16),14-trien-7-one) exhibited potential cytotoxicity against HeLa cell line (IC50 = 23.75 μM).

Development of Comprehensive Online Two-Dimensional Liquid Chromatography/Mass Spectrometry Using Hydrophilic Interaction and Reversed-Phase Separations for Rapid and Deep Profiling of Therapeutic Antibodies.

Monoclonal antibodies (mAb) and related molecules are being developed at a remarkable pace as new therapeutics for the treatment of diseases ranging from cancer to inflammatory disorders. However, characterization of these molecules at all stages of development and manufacturing presents tremendous challenges to existing analytical technologies because of their large size (ca. 150 kDa) and inherent heterogeneity resulting from complex glycosylation patterns and other post-translational modifications. Multidimensional liquid chromatography is emerging as a powerful platform technology that can be used to both improve analysis speed for these molecules by combining existing one-dimensional separations into a single method (e.g., Protein A affinity separation and size-exclusion chromatography) and increasing the resolving power of separations by moving from one dimension of separation to two. In the current study, we have demonstrated the ability to combine hydrophilic interaction (HILIC) and RP separations in an online comprehensive 2D separation coupled with high resolution MS detection (HILIC × RP-HRMS). We find that active solvent modulation (ASM) is critical for coupling these two separation modes, because it mitigates the otherwise serious negative impact of the acetonitrile-rich HILIC mobile phase on the second dimension RP separation. The chromatograms obtained from these HILIC × RP-HRMS separations of mAbs at the subunit level reveal the extent of glycosylation on the Fc/2 and Fd subunits in analysis times on the order of 2 h. In comparison to previous CEX × RP separations of the same molecules, we find that chromatograms from the HILIC × RP separations are richer and reveal separation of some glycoforms that coelute in the CEX × RP separations.

Comprehensive 2D gas chromatography-time-of-flight mass spectrometry with 2D retention indices for analysis of volatile compounds in frankincense (Boswellia papyrifera).

Frankincense gum resin secreted from Boswellia papyrifera was analysed by comprehensive 2D gas chromatography hyphenated with accurate mass time-of-flight mass spectrometry (GC×GC-accTOFMS). Direct multiple injection experiments with stepwise isothermal temperature programming were then performed to construct isovolatility curves for reference alkane series in GC×GC. This provides access to calculation of second dimensional retention indices (2I). More than 500 peaks were detected and 220 compounds mainly comprising monoterpenes, sesquiterpenes, diterpenes and oxygenated forms of these compounds were identified according to their 1I, 2I and accurate mass data. The study demonstrates the capability of GC×GC-accTOFMS with retention data on two separate column phases, as an approach for improved component identification. A greater number of identified and/or tentatively identified terpenoids in this traditional Chinese medicine allow for a more comprehensive coverage of the volatile composition of frankincense.

Sequential Hybrid Three-Dimensional Gas Chromatography with Accurate Mass Spectrometry: A Novel Tool for High-Resolution Characterization of Multicomponent Samples

A novel sequential three-dimensional gas chromatography-high-resolution time-of-flight mass spectrometry (3D GC-accTOFMS) approach for profiling secondary metabolites in complex plant extracts is described. This integrated system incorporates a nonpolar first-dimension (1Dnp) separation step, prior to a microfluidic heart-cut (H/C) of a targeted region(s) to a cryogenic trapping device, directly followed by the rapid reinjection of a trapped solute into a polar second-dimension (2DPEG) column for multidimensional separation (GCnp-GCPEG). For additional separation, the effluent from 2DPEG can then be modulated according to a comprehensive 2D GC process (GC×GC), using an ionic liquid phase as a third-dimension (3DIL) column, to produce a sequential GCnp-GCPEG×GCIL separation. Thus, the unresolved or poorly resolved components, or regions that require further separation, can be precisely selected and rapidly transferred for additional separation on 2D or 3D columns, based on the greater separation realized by these steps. The described integrated system can be used in a number of modes, but one useful approach is to target specific classes of compounds for improved resolution. This is demonstrated through the separation and detection of the oxygenated sesquiterpenes in hop ( Humulus lupulus L.) essential oil and agarwood ( Aquilaria malaccensis) oleoresin. Improved resolution and peak capacity were illustrated through the progressive comparison of the tentatively identified components for GCnp-GCPEG and GCnp-GCPEG×GCIL methods. Relative standard deviations of intraday retentions (1 tR, 2 tR,, and 3 tR) and peak areas of ≤0.01, 0.07, 0.71, and 7.5% were achieved. This analytical approach comprising three GC column selectivities, hyphenated with high-resolution TOFMS detection, should be a valuable adjunct for the improved characterization of complex plant samples, particularly in the area of plant metabolomics.

Dipyrimicin A and B, microbial compounds isolated from Amycolatopsis sp. K16-0194.

In a search for compounds interacting with ergosterol resin, a new compound named dipyrimicin B was isolated from a rare actinomycete strain, Amycolatopsis sp. K16-0194. In addition, another analog, dipyrimicin A, which does not interact with the resin, was also discovered. The structures of the two dipyrimicins were established by comprehensive 1D and 2D NMR and MS analyses and found to contain a unique core structure, a 2,2'-bipyridine skeleton. Dipyrimicin A showed strong antimicrobial and cytotoxic activity, whereas dipyrimicin B displayed distinctly poor antimicrobial and cytotoxic activities.

Chemical constituents of Genista numidica Spach aerial parts and their antimicrobial, antioxidant and antityrosinase activities

A previously undescribed triterpenoid saponin, 3-O-[α-l-rhamnopyranosyl-(1→2)-{β-d-glucopyranosyl-(1→6)-}β-d-galactopyranosyl-(1→2)-β-d-glucuronopyranosyl]-sophoradiol (1), in addition to twenty-nine known constituents (2–30) were isolated from the aerial parts of Genista numidica Spach. Structures elucidation was performed by comprehensive 1D- and 2D-NMR analyses and HRESIMS. The extracts, fractions and isolated compounds were evaluated for their antibacterial, antioxidant and tyrosinase inhibitory activities. The experimental findings indicated that genistin (16), isosalipurpol (27), and koaburaside (29) have moderate to low antibacterial activity against E. faecalis, S. aureus, S. epidermidis and P. aeruginosa bacteria with MICs ranging from 31.2 to 125 μg/mL. Compounds 19 and 27 exhibited a good antiradical activity potential (IC50 11.8 and 11.1 μg/mL, respectively). Only compounds 23, 27 and 28 exhibited low inhibitory effect against mushroom tyrosinase (IC50 from 90.2 to 225.6 μg/mL).