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Isolation and structure elucidation of novel hypotensive agents, Niazinin A, Niazinin B, Niazimicin and Niaziminin A + B from Moringa oleifera: The first naturally occurring thiocarbamates

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Abstract

Novel hypotensive principles, niazinin A 1, niazinin B 2, niazimicin 4 and niaziminin A and B 6+7, have been obtained from the ethanolic extract of the fresh leaves of Moringa oleifera, employing a bioassay-guided isolation procedure. Their structures have been elucidated through spectroscopic (including 2D NMR techniques) and chemical methods. These compounds are mustard oil glycosides which are very rare in Nature and are also the first examples of naturally occurring thiocarbamates.
... The compound was first identified by Faizi et al. as a spasmolytic (by inhibiting acetylcholine and histamine-induced ileal contractions in guinea pigs) and hypotensive agent having bradycardiac effects as seen both in vivo in Wistar rats and in vitro in guinea pigs atria and rabbits aorta (by inhibiting Kþinduced contractions). NZ was also shown to inhibit the spontaneous contractions of the rat uterus, mediating its effects through a muscarinic receptorindependent mechanism [5][6][7]. In addition, NZ was proposed to be a potent chemo-preventive agent in chemical carcinogenesis by Guevara et al. [8]. ...
... The structure of the isolated compound has been established on the basis of high-resolution mass spectrometry, UV spectral data, 1 H-, 13 C-and 2D-NMR. Compared to the previously reported isolation protocol of Faizi et al. [6], the methodology optimized in this work is much simpler, with fewer types of solvents, and less work-up steps, in addition to the exclusion of a preparative RP-HPLC step in favor of a conventional normal phase column chromatography, thus cheaper and readily-available alternative. ...
... In addition, the presence of three hydroxy groups was shown by a pair of doublet of doublet at d5.04 (2 0 OH) and 4.74 (3 0 OH), with the third hydroxyl appearing as a doublet at d 4.87, being slightly hidden by H7 doublet signal at d4.85. Due to the fact that the compound also exists as a thiol-imine tautomer [6], another signal for the benzylic methylene appears also as a doublet at d4.56, and consequently C7 showed two signals at d47.53 and 47.16 [ Fig. 1c]. This is confirmed by the 2D COSY plot [Fig. ...
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Moringa oleifera (MO) is a highly nutritious plant, whose leaves and seed pods are consumed in Africa, Asia, sub-Himalayan regions and South America. A novel ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the standardization of the bioactive thiocarbamate compound from MO, niazimicin (NZ) in seeds and leaves, is developed, optimized and validated according to the International Conference on Harmonization (ICH) guidelines, using desipramine as the internal standard. Multiple reaction monitoring detection of transitions 358.05>106.86 and 266.38 > 193.04 with collision energy of 25V and 40V, respectively were used. A gradient was optimized at 35-55%B in 7 min, where mobile phase A is aqueous 0.1% formic acid and B is 0.1% formic acid in acetonitrile. The method proved to be linear in the range of 0.05-100 μg/mL, precise, robust and accurate, with LOD and LOQ of 0.02 and 0.05 μg/mL, respectively. MO seeds were found to contain double NZ content (620 mg% ±3.2%) compared to leaves, and the methylene chloride fraction of seeds comprised triple the amount in ethyl acetate fraction (450 mg% ± 2.4%). Results emphasize that seeds of MO are a much richer source for NZ than the most commonly edible and marketed leaves extracts. The reported method can be used for standardization and quality control of the seeds and leaves NZ content.
... Therefore, we proposed novel compounds based on niaziminin (M9) to investigate whether the introduction of a hydroxyl group into niaziminin (M9) would enhance its binding affinity to the Mpro. Niaziminin (M9) is a thiocarbamate isolated from the leaves of Moringa oleifera [51]. The presence of an acetoxy group at the 4′-position of niaziminin (M9) is thought to be important for its ability to inhibit the activation of Epstein-Barr virus [52]. ...
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The novel coronavirus 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly worldwide, and new drug treatments for COVID-19 are urgently required. To find the potential inhibitors against the main protease (Mpro) of SARS-CoV-2, we investigated the inhibitory potential of naturally occurring compounds from the plants Moringa oleifera, Aloe vera, and Nyctanthes arbor-tristis, using molecular docking, classical molecular mechanics optimizations, and ab initio fragment molecular orbital (FMO) calculations. Of the 35 compounds that we simulated, feralolide from Aloe vera exhibited the highest binding affinity against Mpro. Therefore, we proposed novel compounds based on the feralolide and investigated their binding properties to Mpro. The FMO results indicated that the introduction of a hydroxyl group into feralolide significantly enhances its binding affinity to Mpro. These results provide useful information for developing potent Mpro inhibitors. Supplementary information: The online version contains supplementary material available at 10.1007/s11224-022-02021-y.
... Bioactivity-guided isolation of MeOH/H2O extracts of Moringa seeds led to the isolation of two compounds, which were elucidated using spectroscopic methods (1D NMR and LC−Orbitrap−MS). Two compounds, niazinin B (1) and 4-(α-L-rhamnosyloxy) benzyl isothiocyanate (2) were further confirmed by comparing their spectroscopic data with those reported in the literature [8,13]. The chemical structures of compounds 1 and 2 are shown in Figure 3. ...
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Due to the side effects of obesity medications, many studies have focused on the natural products used in the daily diet to control weight. Moringa seed pods and leaves are widely used as vegetables or diet supplements due to the high nutrition value. However, no bioactivity-guided anti-adipogenic study was previously conducted. Therefore, a preadipocyte cell line was adopted as the bioactivity assay to identify the anti-adipogenic compounds in the peeled Moringa seed. Two known sulphur-containing compounds (1 and 2) were isolated and identified. Compound 2, 4-(α-l-rhamnosyloxy) benzyl isothiocyanate, showed a great anti-adipogneic effect with an IC50 value of 9.2 μg/mL. The isothiocyanate (ITC) group in compound 2 could be responsible for the inhibitory activity. In addition, a series of compounds with the ITC group were used to further investigate the structure-activity relationship, indicating foods containing ITC derivatives have the potential of being used to control weight.
... This family is made up of only 13 species (Table 2) (Olson, 2002). Among the 13 species, M. oleifera, also known as "the miracle plant" or "the tree of life," has been by far the most studied one, and its leaves and seeds have been chemically characterized and studied for at least the last 30 years (Faizi et al. 1992). Moringa stenopetala, Moringa concanensis, and Moringa peregrina have also been studied, although to a much lesser extent. ...
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As part of the reciprocity arrangement with Alexander von Humboldt Foundation, Germany, CSIR is obliged to grant two awards to internationally renowned German scientists every year. The German award winners are invited to carry out research projects of their own choice at the Indian research institute for a period ranging between 2 weeks to 4 months, extendable upto one year. The research project may be prepared in consultation with the Indian host institute and should be relevant to and falling in the priority/thrust areas of CSIR. 2. Nominations of internationally recognised German scholars, willing to be considered for this prestigious reciprocity award for the year 2010 for spending time in the Indian research institute, are invited for consideration.
The Institute of Health and Tibbi Research, republished under the auspices of the Hamdard National Foundation
  • C J H Dymock
  • D Warden
  • Pharmacographia Hooper
  • Indica
Dymock, C. J. H. Warden and D. Hooper, Pharmacographia Indica, The Institute of Health and Tibbi Research, republished under the auspices of the Hamdard National Foundation, Pakistan, 1890, vol. 1, p. 396.