The methanol stem bark extract of A. boonei and methanol seed extract of P. nitida, were subjected to purification using chromatographic techniques. A. boonei yielded loganic acid (1), sweroside (2) and secoxyloganin (3), while P. nitida afforded (1), akuammidine (4), akuammicine (5) and alstonine (6). The structures of the compounds were elucidated based on their nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HRMS) profiles and comparison with literature data. The antibacterial activities of the compounds were evaluated using the disc diffusion assay with chloramphenicol as the positive control. Alstonine (6) demonstrated weak activity against Pseudomonas aeruginosa and Streptococcus agalactiae with zones of inhibition of 9.3 ± 0.6 and 10.0 ± 0.0 mm, respectively. This is the first report of sweroside (2) and secoxyloganin (3) in A. boonei.

Malaria is a deadly disease that continues to pose a threat to children and maternal well-being. This study was designed to identify the chemical constituents in the ethanolic fruit extract of Azadirachta indica , elucidate the pharmacological potentials of identified phytochemicals through the density functional theory method and carry out the antimalarial activity of extract using chemosuppression and curative models. The liquid chromatography-mass spectrometry (LC-MS) analysis of the ethanolic extract was carried out, followed by the density functional theory studies of the identified phytochemicals using B3LYP and 6-31G (d, p) basis set. The antimalarial assays were performed using the chemosuppression (4 days) and curative models. The LC-MS fingerprint of the extract led to the identification of desacetylnimbinolide, nimbidiol, O-methylazadironolide, nimbidic acid, and desfurano-6α-hydroxyazadiradione. Also, the frontier molecular orbital properties, molecular electrostatic potential, and dipole moment studies revealed the identified phytochemicals as possible antimalarial agents. The ethanolic extract of A indica fruit gave 83% suppression at 800 mg/kg, while 84% parasitaemia clearance was obtained in the curative study. The study provided information about the phytochemicals and background pharmacological evidences of the antimalarial ethnomedicinal claim of A indica fruit. Thus, isolation and structure elucidation of the identified phytochemicals from the active ethanolic extract and extensive antimalarial studies towards the discovery of new therapeutic agents is recommended for further studies. Keywords Malaria , , , liquid chromatography-mass spectrometry , density functional theory , chemosuppression , curative

Malaria is a deadly disease that continues to pose a threat to children and maternal well-being. This study was designed to identify the chemical constituents in the ethanolic fruit extract of Azadirachta indica, elucidate the pharmacological potentials of identified phytochemicals through the density functional theory method and carry out the antimalarial activity of extract using chemosuppression and curative models. The liquid chromatography-mass spectrometry (LC-MS) analysis of the ethanolic extract was carried out, followed by the density functional theory studies of the identified phytochemicals using B3LYP and 6-31G (d, p) basis set. The antimalarial assays were performed using the chemosuppression (4 days) and curative models. The LC-MS fingerprint of the extract led to the identification of desacetylnimbinolide, nimbidiol, O-methylazadironolide, nimbidic acid, and desfurano-6α-hydroxyazadiradione. Also, the frontier molecular orbital properties, molecular electrostatic potential, and dipole moment studies revealed the identified phytochemicals as possible antimalarial agents. The ethanolic extract of A indica fruit gave 83% suppression at 800 mg/kg, while 84% parasitaemia clearance was obtained in the curative study. The study provided information about the phytochemicals and background pharmacological evidences of the antimalarial ethnomedicinal claim of A indica fruit. Thus, isolation and structure elucidation of the identified phytochemicals from the active ethanolic extract and extensive antimalarial studies towards the discovery of new therapeutic agents is recommended for further studies.

There is explored, herein, functional relation: Experimental mass spectrometric phenomenon, obeying a certain scientific law ⇔ 3D molecular conformations and electronic structures of analytes obtained for quantum chemical theories. The paper answers to questions: (a) What evidence claims these actual relations among measurable and theoretical parameters, experimental factors and molecular properties; (b) how the provided evidence is collected and used; and (c) how empirical proof relates to assign and explain mass spectrometric phenomena of steroids afforded by our innovative stochastic dynamic mass spectrometric formula, D″SD = 2.6388.10-17.(-2), quantum chemical 3D conformations, electronic structures and energetics of molecules, respectively. The paper address issue concerning empirical evidence at very high-to-exact level of assignment of 3D molecular conformations of steroids to experimental mass spectrometric fragment ions, accounting precisely for (i) effect of protonation; (ii) intramolecular rearrangement for A-D rings of steroidal skeleton and proton transfer effect, if any; in addition to (iii) examination of enantiomers of steroids in mixture with different stereochemistry, (R) and (S), of a set of six atoms of the molecular backbone of hydrocortisone (1), deoxycorticosterone (2), progesterone (3) and methyltestosterone (4), respectively. Results from testosterone (5) are discussed, as well. There are used ultra-high resolution atmospheric pressure chemical ionization mass spectrometric data on analytes (1)-(4) at ng.(mL)-1 concentration levels in mixtures in solution obtained for positive operation mode. High accuracy static and molecular dynamic quantum chemical computations and chemometrics are also utilized. Experimental 3D structural parameters of steroids obtained for stochastic dynamic diffusion theory are correlated with available crystallographic data.

Chemical investigation of the root of Zanthoxylum paracanthum afforded 1 new alkamide derivative, (2E,4E)-6-oxo-N-isobutyldeca-2,4-dienamide (1) together with 10 known congeners including one phenolic amide (2), four benzophenanthridines (3 - 6), three indolonaphthyridines (7 - 9) and two lignans (10 and 11). Their structures were elucidated by a combination of spectroscopic and spectrometric data. Using resazurin reduction assay, the crude extract (10 mu g/mL) and isolates (10 mu M) were screened for their cytotoxic activities against the drug-sensitive (CCRF-CEM) leukemia cell line and its multidrug-resistant counterpart (CEM/ADR5000). Compounds 3, 4 and 6 showed cytotoxicity against CCRF-CEM with IC50 values of 2.00 +/- 0.33, 2.31 +/- 0.20 and 0.11 +/- 0.04 mu M, respectively. Only compound 6 exhibited strong cytotoxic activity against CEM/ADR5000 with an IC50 value of 2.34 +/- 0.34 mu M in comparison with the standard drug doxorubicin which showed IC50 values of 0.01 +/- 0.14 (CCRF-CEM) and 26.78 +/- 3.30 mu M (CEM/ADR5000).

The paper presents innovative stochastic dynamic formulas treating quantitatively mass spectrometric outcome intensity by introducing diffusion coefficient, which is used to quantify and determine 3D structurally solvate inorganics of Zn-II-ion observed under electrospray ionization conditions of metal-organics of 5-sulfosalicylic acid (1), 3,4-dihydroxy benzoic acid (2) and quinolin-8-ol (3), due to ligand exchange reactions of {[Zn-II(H2O)(6)](2+))} and {[(ZnCl4)-Cl-II](2-)} counterions, determined by single crystal X-ray diffraction. The diffusion data are applied to multidimensional structural analysis using correlatively quantum chemical diffusion data according to Arrhenius's theory. We provide empirical proof of validity of a new simplistic derived equation D-SD('') = 2.6388.10(-17) (-()(2)) to inorganics. The degree of testability of our formulas is justified by means of independent single crystal X-ray diffraction data. Insights into coordination chemistry of Zn-II-ion in solution are gained. High accuracy quantum chemical static methods and molecular dynamics are utilized, as well.

Tetrapleura tetraptera is a medicinal plant used in East and West Africa to treat inflammation and related diseases. From the stem bark of the plant, three previously undescribed flavan-3-ol derivatives named (2R,3S)-3,3 ',5 ',7-tetrahydroxy-4 '-methoxyflavane (1), (2R,3S)-3 ',5 ',7-trihydroxy-4 '-methoxyflavane-3-O-beta-D-glucopyranoside (2), and (2R,3S,4S)-3,3 ',4,5 ',7-pentahydroxy-4 '-methoxyflavane (3) were isolated with three known analogues. The structural elucidation of the compounds was performed based on NMR spectroscopy and HRMS data analyses. The absolute configurations around the stereogenic carbons were determined using Circular Dichroism (ECD) and density functional theory (DFT) calculations. The cytotoxicity of the isolated compounds was tested using resazurin reduction assay. Compound 1 was moderately active against both recalcitrant leukemia cell lines with IC50 values of 21.90 mu M towards CCRF-CEM and 50.80 towards CEM/ADR5000. Similar level of activity was observed for compound 3 against CCRF-CEM cell line, IC50 = 35.50 mu M. All the tested compounds were not cytotoxic compared with the standard drug, doxorubicin, with IC50 values of 0.0075 against CCRF-CEM and 24.30 mu M against CEM/ADR5000.

From the leaves of Kenyan medicinal plant Bersama abyssinica Subspecies abyssinica, four previously undescribed compounds namely, three bufadienolides, 10 beta-formylpaulliniogenin B, 10 beta-formylpaulliniogenin A and 1 beta-acetoxy-3 beta,5 beta-dihydroxy-15-methoxy-16,19-dioxobufa-14(15),20,22-trienolide, and a phenolic compound 2,6,4'-trihydroxybenzophenone-4-O-(6'''-cinnamoyl)-beta-D-glucoside were isolated together with four known compounds. The structural elucidation of the compounds was based on 1D and 2D NMR spectroscopy and HRMS data analyses. The relative configurations were defined by NOESY correlations. Cytotoxic activities on L929 and KB3.1 cell lines of the isolated compounds were investigated using MTT assay. The 1 beta-acetoxy-3 beta,5 beta-dihydroxy-15-methoxy-16,19-dioxobufa-14(15),20,22-trienolide showed significant cytotoxic activity against KB3.1 cell lines with IC50 of 3.9 +/- 0.99 mu M.

This study addresses the problem of performing mass spectrometric (MS), 3D molecular and electronic structural analyses of glycans mixtures from fetal bovine serum. This undertaking is unexpectedly difficult, due to: random variation of non-template-driven glycosylation and fucosylation processes; a lack of regioselective derivatization for mixtures of polydisperse glycans towards length and skeletal modifications; isomers of oligomers and polymers, including linear and branching molecular structures, respectively. These factors significantly increase the difficulty in glycan structural analysis using mass spectrometry. Furthermore, MS phenomena of carbohydrates include reactions of intramolecular rearrangement and cyclization, proton and charge transfer effects, noncovalently bound self-associations, alkali metal ion adducts, and multiply charged species under the tandem MS/MS operation mode. However, this study presents a plausible solution to the problem. It employs our innovative stochastic dynamic MS model formula D”SD = 2.6388.10−17. (–2) that is capable of accurately quantifying the fluctuations and temporal behavior of measurable variable intensity (I) of analyte peaks. It has been shown that it can accurately and directly quantify analyte concentrations in solution and determine 3D molecular and electronic structures. This latter task is less straightforward. It employs the Arrhenius model equation within the framework of his transition state theory and the power capability of quantum chemical methods. The validity of the latter statements is examined, herein. This study, first, comes to grips with MS collision-induced dissociation phenomena of mixtures of 2-aminobenzamide-derivatized glycans. It utilizes ab initio and DFT static, molecular dynamics, molecular mechanics, and chemometrics.

The major goal of the paper is to provide empirical proof of view that innovative stochastic dynamic mass spectrometric equation D ″ SD = 2.6388·10 −17 ·(< I 2 > − < I > 2 ) determines the exact analyte concentration in solution via quantifying experimental variable intensity ( I ) of an analyte ion per any short span of scan time of any measurement, which also appears applicable to quantify laser-induced ultraviolet photofragmentation and high energy collision dissociation mass spectrometric processes. Triadimenol (1) and sucralose (2) using positive and negative polarity are examined. Laser irradiation energy λ ex = 213 nm is utilized. The issue is of central importance for monitoring organic micro-pollutants in surface, ground, and drinking water as well as tasks of risk assessment for environment and human health from contamination with organics. Despite the significant importance of the topic, answering the question of functional kinetic relations of such processes is by no means straightforward, so far, due to a lack of in-depth knowledge of mechanistic aspects of fragment paths of analytes in environment and foods as well as kinetics of processes under ultraviolet laser irradiation. Although there is truth in the classical theory of first-order reaction kinetics , it does not describe all kinetic data on analytes (1) and (2). A new damped sine wave functional response to a large amount of kinetics is presented. High-resolution mass spectrometric data and chemometrics are used. The study provides empirical evidence for claim that temporal behavior of mass spectrometric variable intensity under negative polarity obeys a certain scientific law written by means of equation above. It is the same for positive and negative soft-ionization mass spectrometric conditions.

Experimental MALDI-MS spectra in solid-state associated with the entitled publication.

Even though maytansine was first discovered from Celastraceae plants, it was later proven to be an endophytic bacterial metabolite. However, a pure bacterial culture cannot synthesize maytansine. Therefore, an exclusive interaction between plant and endophytes is required for maytansine production. Unfortunately, our understanding of plant–endophyte interaction is minimal, and critical questions remain. For example: how do endophytes synthesize maytansine inside their plant host, and what is the impact of maytansine production in plant secondary metabolites? Our study aimed to address these questions. We selected Gymnosporia heterophylla as our model and used amino-hydroxybenzoic acid (AHBA) synthase and halogenase genes as biomarkers, as these two genes respond to biosynthesize maytansine. As a result, we found a consortium of seven endophytes involved in maytansine production in G. heterophylla, based on genome mining and gene expression experiments. Subsequently, we evaluated the friedelin synthase (FRS) gene’s expression level in response to biosynthesized 20-hydroxymaytenin in the plant. We found that the FRS expression level was elevated and linked with the expression of the maytansine biosynthetic genes. Thus, we achieved our goals and provided new evidence on endophyte–endophyte and plant–endophyte interactions, focusing on maytansine production and its impact on plant metabolite biosynthesis in G. heterophylla.

The study reports quantification of metronidazole (MTZ) in clinical human urine employing our innovative stochastic dynamic equation D"(SD) =2.6388.10(-17).(-). There are direct analysis without presence of internal standard, using ultra-high accuracy nano-electrospray ionization (ESI) mass spectrometry (MS), quantum chemistry and chemometrics, respectively. The linear calibration D"(SD) =f(conc.) equations are obtained for concentration range 2.5 to 25000 ng.(mL)(-1) of spiked urine samples, examining analyte MS ions at m/z 171.099(8), 172.071(8), 172.040(81), 213.146(3), 181.07(22) and 151.111(4), respectively. There is achieved exact coefficient of linear correlation (|r|=1) between theory and experiment of ion at m/z 172.0408(1). The major challenge to quantify MTZ in urine sample is that it stabilizes cations [M+H](+) of two tautomers, which equilibrium varies drastically within the standard linear calibration dynamic range. The fragmentation patterns depend on analyte tautomers and it unambiguous assignment in multicomponent samples with complex sample matrix effect (SME) is unable to be made without mediation to an independent physico-chemical law. To solve the problem, herein, is used, again, above equation, which is designed a bridge between quantitative and multidimensional structural analytical chemistry, when is used complementary with Arrhenius's quantum chemical diffusion parameter (D-QC.) There is achieved |r|=0.98 of D"(SD)=f(D-QC') examining tautomeric molecular and fragment ions of MTZ.

The study provides new function tested on labetalol in large infusion volumes (V-inf = 80-115 & mu;L) via electrospray ionization mass spectrometry, tandem MS2-MS7 operation modes and collision energy: 0, 0.1, 10, 20, 25, 26, 30 and 35 eV, respectively. It is derived from the stochastic dynamic mass spectrometric equation D"(SD) = 2.6388.10(-17).(-(2)), which exactly quantifies analyte concentration in solution. Also, it determines 3D conformations and electronic structures. The description of mass spectrometric intensity data as random variables and the shown relation, there are written two new linear functions among D"(SD) parameters, average total intensity values of fragmentation peaks, infusion volume, and collision energy. They introduce covariance of datasets of variables per short span of scan time of ions in any experimental conditions "l" and "m". They are: D"(SD;m,l) = D"(SD,l) + D"(SD,m) + 5.2776.10(-17).{-.}& AP;+ and +& AP;|r(l,m)|.sd(yEr & PLUSMN;)(1).sd(yEr & PLUSMN;)(m). Those relations yields to new formula D"(SD,l)+ D"(SD,m) = |r(l,m)|.sd(yEr & PLUSMN;)(l).sd(yEr & PLUSMN;)(m), providing exact function of mass spectrometric variable intensity of any peaks of analyte ion in any two sets of experimental conditions of measurements and diffusion parameters according to the first formula. Correlation between theory and experiment of fragmentation processes of labetalol shows |r|=1-0.99999. Chemometrics is used.

Experimental ESI(+)-MS/MS data on the entitled compound. Supporting information file for publishing contribution.

During production of diethylenetriaminepentaacetic acid (DTPA), process waste water is generated in several production stages. Process wastewater is usually disposed of via waste water treatment plants. However, due to low biodegradability of DTPA in conventional waste water treatment, incineration constitutes the current method of choice. The main disadvantage of incineration is high consumption of primary energy sources leading to substantial emission of carbon dioxide (CO2). Thus, an alternative method of process waste water treatment was investigated, which consists of an initial application of ozone and a subsequent biological treatment. In 2009, preliminary laboratory experiments were conducted to evaluate the elimination of DTPA in process waste water. Based on the initial results, the responsible authorities granted approval for large-scale ozonation of DTPA-containing wastewater in 2011. Additional laboratory scale experiments were carried out to assess the elimination of the target compound and the generation of its main transformation products using liquid chromatography - high resolution mass spectrometry. Through application of the postulated method, the concentration of DTPA and its derivatives can be reduced to levels assuring safe discharge into the receiving water. Additionally, a comparison of CO2 emissions showed that ozonation is an ecological alternative to incineration and, most likely, an economical as well, based on the local prices of primary energy sources.

Background: Leukemia is the most common type of childhood cancer. Numerous flavonoids isolated from plants have been reported as potential chemotherapeutic agents against malignant growth while taking care of healthy cells. Purpose: To discover new anticancer agents from the seeds of Dracaena steudneri Engl for their potential uses as candidate compounds against leukemia cell lines. Methods: A panel of chromatography techniques (CC, Sephadex LH-20 and semi-preparative HPLC) were used to isolate these compounds from the MeOH/CH2Cl2 (1:1) crude extract of the seeds of D. steudneri. Their structure elucidation was achieved based on spectral evidence (UV, NMR and HRESIMS). Resazurin reduction assays were performed to assess the cytotoxicity of the crude extract and isolates. Results: From the seeds of D. steudneri 8 compounds were isolated (1 – 8). Quercetin derivatives: 3,3′-di-O-methylquercetin-4′-O-β-D-glucoside (5) and 3,3′-di-O-methylquercetin (7) displayed significant cytotoxicity against the two leukemia cell lines tested with IC50 < 10 µM. Doxorubicin (reference drug) exhibited strong cytotoxic potency; IC50 of 0.01 µM (against CCRF-CEM cells) and moderate activity; IC50 of 26.78 µM (towards CEM/ADR5000 cells). To the best of our knowledge, this is the first report of flavonoids glycosides from the genus Dracaena. Conclusion: The results obtained in this study showed that flavonoids isolated from Dracaena steudneri are promising candidates for cancer chemotherapy. The mode of action and the cytotoxicity of the most active compounds (5 and 7) should be further investigated.