High-resolution Mass Spectral Research Articles

Synthesis, characterization and pharmacokinetic studies of 4-(3-aryl-1, 6-dihydro-6-iminopyridazin-1-yl)butanoic acid hydrochlorides

A series of six title compounds have been prepared using 3-amino- 6-chloropyridazine as starting material collected from commercial sources and were characterized by IR, 1H NMR, and high-resolution mass spectral (HRMS) data. The method involves three steps: Suzuki-Miyaura cross-coupling reaction, N(2)-alkylation, and acid hydrolysis, respectively, to obtain final products with good yields. According to Lipinski's rule of five and Veber's rule, pharmacokinetics studies of the synthesized compounds showed that all the parameters were in between the permissible limits. The toxicity parameters were low for the compounds to act as drugs.
 J. Bangladesh Acad. Sci. 45(1); 37-47: June 2021

Ethnomedicinal documentation and anti-inflammatory effects of n-butanol extract and of four compounds isolated from the stems of Pituranthos scoparius: An in vitro and in vivo investigation

Ethnopharmacological relevancePituranthos scoparius is a medicinal plant belonging to the Apiaceae family. It thrives in North Africa, and is widely distributed in the high plateau of most parts of the Sahara in Algeria. This plant is widely used in the Algerian traditional medicine to treat numerous infectious diseases, dermatoses, nervous breakdowns, digestive disorders, and calm abdominal pain. Aim of the studyThe aim of the present work was to examine the ethnomedicinal uses of Pituranthos scoparius in Setif region, Algeria, isolate and identify the chemical constituents of the n-butanol stem extract of P. scoparius (BEPS), and to determine the toxicity and anti-inflammatory effects of these compounds in addition to the extract. Materials and methodsThe anti-inflammatory effects of BEPS and the four compounds isolated from the extract were evaluated using the in vitro protein denaturation assay, whereas the topical anti-inflammatory activity was assessed using the croton oil-induced ear edema in mice. Toxicity was determined based on assessment of in vitro cytotoxicity using hemolytic activity against human red blood cells (RBCs). ResultsFour compounds, identified as the rare isorhamnetin-3-O-β-apiofuranosyl (1 → 2)-β glucopyranoside (2), in addition to three known compounds, namely isorhamnetin-3-O-β-glucoside (1), D-mannitol (3), and isorhamnetin-3-O-β-glucopyranosyl-(1 → 6)-β-glucopyranoside (4) were isolated from BEPS. These compounds were characterized by means of NMR and high-resolution mass spectral (HRMS) data. These four compounds were isolated for the first time from this traditional Algerian medicinal plant. Screening of the extract indicated the presence of alkaloids, polyphenols, flavonoids, free quinones, coumarins and tannins. Topical anti-inflammatory effect showed that the four isolated compounds, as well as BEPS, exhibit a significant (p < 0.05) dose-dependent (0.5 and 1 mg/ear) anti-inflammatory effect. At a dose of 1 mg/ear, compounds 1, 2, and 4, exhibited remarkable anti-inflammatory effect with a percentage inhibition of 85.50 ± 2.78, 79.78 ± 4.68, and 75.78 ± 2.98%, respectively. Results from in vitro cytotoxicity showed that the % lysis of the extract, along with isolated compounds was found to be virtually nontoxic. ConclusionsThese results suggest that BEPS and isolated compounds are safe, nontoxic, and exert remarkable anti-inflammatory effects, and can be new sources of natural anti-inflammatory agents.

A new phthalide derivative from Peperomia nivalis

One new phthalide (1) was isolated from aerial parts of Peperomia nivalis, along with known compounds (2 and 3), reported in this species for the first time. The structure of the new compound was characterised on the basis of 1D (1H and 13C NMR), 2D (COSY, HMQC, HMBC and NOESY) NMR and high-resolution mass spectral (HRMS) data. Compound 2 was isolated from a natural source for the first time but previously synthesised. Compounds 1–3 were evaluated for their anti-Helicobacter pylori and anti-Plasmodium falciparum activities. Compound 1 showed moderate activities against H. pylori (MIC 47.5 μM) and the F32-Tanzania strain of P. falciparum (IC50 8.5 μM). Compounds 2 and 3 exhibited weak anti-H. pylori activity (MIC 241.3 and 237.6 μM, respectively) and were inactive against P. falciparum.

A New Cucurbitane Glycoside from Siraitia grosvenorii

A systematic phytochemical study of the commercial extract of Luo Han Guo (Siraitia grosvenorii) resulted in the isolation of an additional minor new cucurbitane glycoside, mogroside V Al (1). The structure of the new compound was characterized on the basis of 1D (1H and 13C NMR) and 2D (COSY, HMQC, HMBC and NOESY) NMR and high resolution mass spectral (HRMS) data, as well as hydrolysis studies.

HPLC–HRMS method for fast phytochelatins determination in plants. Application to analysis of Clinopodium vulgare L.

An optimized analytical method based on C8 core-shell reverse phase chromatographic separation and high resolution mass spectral (HRMS) detection is developed for a fast analysis of unbound phytochelatins (PCs) in plants. Its application to analysis of Clinopodium vulgare L. is demonstrated where proper PCs liberating and preservation conditions were employed using dithiotreitol in the extraction step. A baseline separation of glutathione (GSH) and phytochelatins from 2 to 5 (PC2–PC5) for 3min was achieved at conventional HPLC backpressure, with detection limits from 3ppt (for GSH) to 2.5ppb (for PC5). It is shown, that the use of HRMS with tandem mass spectral (MS/MS) capabilities permits additional wide range screening ability for iso-phytochelatins and PC similar compounds, based on exact mass and fragment spectra in a post acquisition manner.

Acylated Flavonoid from Vaccinium Corymbosum (Ericaceae) Flowers with Yeast α-Glucosidase Inhibitory Activity

Purpose: To isolate and identify chemical constituents with yeast α-glucosidase inhibitory activity from the methanol extract of V. myrtillus (blueberry) flowers.Methods: The active fraction (ethyl acetate extract) were chromatographed on C18 MPLC column, Sephadex LH-20 column and semi-preparative HPLC column. The isolated compounds were identified by the extensive 1H-nuclear magnetic resonance spectroscopy (NMR), 13C-NMR, 2D-NMR and high resolution mass spectral (HR-MS) analyses.Results: Two phenolic compounds, an acylated flavonoid and a coumaric acid derivative, were isolated and identified as isorhamnetin-3-O-(6''-O-coumaroyl)-β-D-glucoside (1) and cis-cinnamic acid methyl (2). Compound 1 showed powerful α-glucosidase inhibitory activity and in this regard, was superior to the positive drug, acarbose.Conclusion: Compounds 1 and 2 were isolated for the first time from this species and the genus of Vaccinium. This is the first report on characterization of these phenolic compounds and the possible utilization of blueberry flowers for nutraceutical and functional food applications.Keywords: Vaccinium corymbosum, Blueberry, Acylated flavonoid, Yeast α-Glucosidase, Inhibitory activity, Nutraceuticals

Highly selective and sensitive colourimetric detection of Hg2+ ions by unsymmetrical squaraine dyes

Abstract A novel class of sulphonate group containing unsymmetrical squaraine dyes has been synthesized. These dyes show a selective and sensitive affinity towards Hg2+ in methanol and are practically insensitive to most other environmentally and biologically relevant metal ions. Isothermal titration calorimetric (ITC) studies and High Resolution Mass Spectral (HRMS) analysis indicate a 1:1 binding mode. 1H and 13C NMR of the isolated Dye…Hg2+ adduct showed an unusual addition reaction of Hg2+ along the phenyl-squarate carbon–carbon bond which was also supported by TD-DFT calculations using PM6 level geometries.

Synthesis and Characterization of New Thebaine Derivatives: 2-(6,14-endo-Ethenotetrahydrothebaine-7α;-yl)-5-(N-Arylamino)-1,3,4-Thiadiazoles

We have synthesized a series of novel 2-(6,14-endo-ethenotetrahydrothebaine-7α-yl)-5-N-arylamino-1,3,4-thiadiazoles (5a–n) as potential narcotic analgesics, which are analogs of morphine. The synthesized compounds exhibit rigid morphine structures, including a 6,14-endo-entheno bridge and a 5-N-arylamino-1,3,4-thiadiazol-2-yl group at C-7 position that adopted S-configuration. The structures and stereochemistry of the compounds were completely assigned using one- and two-dimensional NMR experiments (1H NMR, APT, COSY, NOESY, HMQC, and HMBC), FTIR, and high-resolution mass spectral (HRMS) data. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.

Spectral Analysis and Chemical Studies of the Sweet Constituent, Rebaudioside A

Aim: To study NMR spectral analysis and hydrolysis products of Rebaudioside A ( 1) that has been isolated from Stevia rebaudiana. Study Design: Acquiring NMR and high resolution mass spectral (HRMS) data of Rebaudioside A for structural characterization, and identification of hydrolysis products. Place of Study : Organic Chemistry Department of The Coca-Cola Company, Atlanta, GA 30313, USA. Methodology: The 1D ( 1 H & 13 C) and 2D (COSY, HSQC, and HMBC) NMR spectral data of was acquired using Varian Unity Plus 600 MHz instrument using standard pulse sequences. Hydrolysis studies were performed on Rebaudioside A using acid, base and enzymatic studies to identify partial degradation products, aglycone and sugar residues. Results: The proton and carbon values of Rebaudioside A were assigned based on NMR and HRMS data as well as chemical studies. The aglycone was identified as steviol on the basis of enzymatic hydrolysis, sugar was identified as D-glucose from acid hydrolysis and the partial hydrolyzed product was identified as Rebaudioside B from alkaline hydrolysis.

Synthesis and Evaluation of Anti-inflammatory and Analgesic Activities of a Novel Series of Coumarin Mannich Bases

A novel series of coumarinyl Mannich bases (3a-1) have been synthesized by reacting 3-acetyl coumarin (1) with various substituted secondary amines (2a-1) in presence of paraformaldehyde. The structures of the newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR and HRMS (high resolution mass spectral) data. Title compounds were screened for in vivo acute anti-inflammatory activity using the carrageenan-induced rat paw edema assay model. Among the compounds tested, 3-[3-(diethylamino)propanoyl]-2H-chromen-2-one (3a)and 3-[3-(piperidine-1-yl) propanoyl]-2H-chromen-2-one (3c) showed 63.1 and 66.7% inhibition, respectively, as compared to the standard drug diclofenac (CAS 15307-86-5, 68.8%). These potent compounds showed encouraging analgesic andantipyretic activities.