- Neuroprotective evaluation of novel substituted 1,3,4-oxadiazole and aroylhydrazone derivatives
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The paper reports on the facile and convenient synthesis of a series of novel 2,5-substituted 1,3,4-oxadiazoles 3a-f and that of aroylhydrazone-based molecular hybrids 5a-g from readily available starting materials. The structure of the compounds was confirmed by IR, 1H NMR, 13C NMR and HRESI-MS spectral data. The toxicological potential of the compounds was evaluated by monitoring the synaptosomal viability and the levels of reduced glutathione in rat brain synaptosomes, isolated by Percoll gradient. The neuroprotective effects were assessed in vitro in a model of 6-hydroxydopamine-induced neurotoxicity. Administered alone, at a concentration of 40 μM, most of the 1,3,4-oxadiazole derivatives and all of the hydrazone derivatives exhibited weak statistically significant neurotoxic effects, compared to the control. Two of the compounds from the novel oxadiazoles 3a and 3d did not have any toxicity. In a model of 6-OHDA-induced oxidative stress, again 3a and 3d and all aroylhydrazone derivatives 5a-g revealed statistically significant neuroprotective effect by preserving the synaptosomal viability and the level of reduced glutathione, against the toxic agent. Some of the compounds may have neuroprotective effects due to possible stabilization of the synaptosomal membrane and/or because of the preserved reduced glutathione. Additionally, all the compounds display a good predicted ADME profile.
- Angelova, Violina T.,K.-Yovkova, Elena,Karabeliov, Valentin R.,Kondeva-Burdina, Magdalena S.,Vassilev, Nikolay G.
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supporting information
(2022/01/20)
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- Discovery of Pimprinine Alkaloids as Novel Agents against a Plant Virus
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Plant viral diseases cause tremendous decreases in crop yield and quality. Natural products have always been a valuable source for lead discovery in medicinal and agricultural chemistry. A series of pimprinine alkaloids and their derivatives were prepared and identified by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HR-MS). The antiviral activities of these alkaloids against tobacco mosaic virus (TMV) were systematically investigated for the first time. Most of the compounds exhibited higher antiviral activities than ribavirin. Compounds 5l, 9h, and 10h, which had similar or higher antiviral activities than ningnanmycin (perhaps the most widely used antiviral agent at present), emerged as new antiviral pilot compounds. This systematic structure-activity-relationship research lays the foundation for simplifying the structure of these alkaloids. The ring-open products, acylhydrazones 9a-9u, were also found to possess good antiviral activities. Moreover, all the synthesized compounds displayed broad-spectrum fungicidal activities. This study provides important information for the research and development of pimprinine alkaloids as novel antiviral agents.
- Liu, Bin,Li, Rui,Li, Yanan,Li, Songyi,Yu, Jin,Zhao, Binfen,Liao, Ancai,Wang, Ying,Wang, Ziwen,Lu, Aidang,Liu, Yuxiu,Wang, Qingmin
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p. 1795 - 1806
(2019/02/27)
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- An efficient synthesis and biological study of novel indolyl-1,3,4-oxadiazoles as potent anticancer agents
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A facile, convenient and high yielding synthesis of a series of novel 5-(3′-indolyl)-2-(substituted)-1,3,4-oxadiazoles from readily available starting materials has been described. The key step of this protocol is oxidative cyclization of N-acylhydrazones
- Kumar, Dalip,Sundaree, Swapna,Johnson, Emmanuel O.,Shah, Kavita
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scheme or table
p. 4492 - 4494
(2010/04/05)
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- Synthesis and properties of azoles and their derivatives. 33. Synthesis of 1,3,4-oxadiazoles that contain an indolyl group
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2,5-Disubstituted oxadiazoles with indole residues were synthesized by condensation of the hydrochlorides of the corresponding imido esters with hydrazines, as well as by cyclization of hydrazides by the action of POCl3. 2-Substituted oxadiazoles of the same series were obtained by condensation of the corresponding hydrazides with ethyl orthoformate.
- Kelarev,Shvekhgeimer
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p. 258 - 261
(2007/10/02)
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