New GABA-modulating 1,2,4-oxadiazole derivatives and their anticonvulsant activity

Lankau, Hans‐Joachim; Unverferth, K.; Grunwald, Christian; Hartenhauer, Helge; Heinecke, Kristina; Bernöster, Katrin; Dost, R.; Egerland, Ute; Rundfeldt, Chris

doi:10.1016/j.ejmech.2006.12.022

Cited by 68 publications

(36 citation statements)

References 17 publications

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“…The isotropic magnetic shielding (IMS) values calculated using the GIAO approach at the 6-31G (d,p) level were used to predict the 13 C-and 1 H-NMR chemical shifts (δ calc ) for compound 4; results were in agreement with the experimental NMR data (δ exp ) in CDCl 3 . The experimental and theoretical 1 H-and 13 C-NMR chemical shifts of the studied compound are presented in Table S2 (Supplementary Material).…”

Section: Nmr Spectrasupporting

confidence: 66%

“…The extent of MTT reduction to formazan within cells was calculated by measuring the absorbance at 570 nm using a micro plate reader (Spectra Max plus, Molecular Devices, CA, USA). Cytotoxicity was recorded as the concentration causing 50% growth inhibition (IC 50 ) for PC 3 and HeLa cancer cells. The percent inhibition was calculated by using the following formula: …”

Section: Cytotoxicity Activity By Using Mtt Assaymentioning

confidence: 99%

“…Pharmaceutical drugs based on bioactive natural products or small synthetic molecules are still the backbone of cancer therapy, with main cellular targets including tubulin, DNA, and several protein kinases [1][2][3]. Therefore, synthesis of new small organic compounds with selective activity against cancerous cells is the center of attention of anticancer drug development.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis, Molecular Structure Optimization, and Cytotoxicity Assay of a Novel 2-Acetyl-3-amino-5-[(2-oxopropyl)sulfanyl]-4-cyanothiophene

et al. 2016

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Abstract:A novel thiophene-containing compound, 2-acetyl-3-amino-5-[(2-oxopropyl)sulfanyl]-4-cyanothiophene (4) was synthesized by reaction of malononitrile with CS 2 in the presence of K 2 CO 3 under reflux in DMF and the subsequent reaction with chloroacetone followed by cyclization. This compound has been characterized by means of FT-IR, 1 H-NMR, 13 C-NMR, and mass spectrometry as well as elemental analysis. In addition, the molecular structures of compound 4 was determined by X-ray crystallography. The geometry of the molecule is stabilized by an intramolecular interaction between N1-H1¨¨¨O1 to form S6 graf set ring motif. In the crystal, molecules are linked via N1-H2¨¨¨O1 and C7-H7A¨¨¨N2 interactions to form a three-dimensional network. Molecular structure and other spectroscopic properties of compound 4 were calculated using DFT B3LYP/6-31G (d,p) method. Results revealed a good agreement between the optimized geometric parameters and the observed X-ray structure. Furthermore, and by employing the natural bond orbital (NBO) method, the intramolecular charge transfer (ICT) interactions along with natural atomic charges at different sites, were calculated; results indicated strong nÑπ* ICT from LP(1)N5ÑBD*(2)C15-C16 (63.23 kcal/mol). In addition, the stabilization energy E(2) of the LP(2)O3Ñ BD*(1)N5-H6 ICT (6.63 kcal/mol) indicated the presence of intramolecular N-H¨¨¨OH bonding. Similarly, calculations of the electronic spectra of compound 4 using, TD-DFT revealed a good agreement with the experimental data. Finally, compound 4 was evaluated for its in vitro cytotoxic effect against PC-3 and HeLa cell lines, as an anticancer agent, and found to be nontoxic.

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Section: Nmr Spectrasupporting

confidence: 66%

Section: Cytotoxicity Activity By Using Mtt Assaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synthesis, Molecular Structure Optimization, and Cytotoxicity Assay of a Novel 2-Acetyl-3-amino-5-[(2-oxopropyl)sulfanyl]-4-cyanothiophene

et al. 2016

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“…The best known mechanisms that result in anticonvulsant activity are the potentiation of GABA (γ-aminobutyric acid) and the lock of the sodium channel (Lankau et al, 2007).…”

Section: Anticonvulsant Activitymentioning

confidence: 99%

“…Three trial models, the MES test, PTZ test and the rotarod were used in rats by Lankau et al (2007) to obtain the characterization of primary compounds and a first clue to the effectiveness and safety of 1,2,4-oxadiazole synthesized (Table 7). All synthesized compounds with in vivo activity, potentiated the induced GABA currents in rat cortical neurons, however, without interaction with the benzodiazepine site, which is usually expected for this positive modulation.…”

Section: Anticonvulsant Activitymentioning

confidence: 99%

1,2,4-oxadiazole: A Brief Review from the Literature About the Synthesis and Pharmacological Applications

Rosa¹,

Morcelli²,

Lobo³

2015

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Este trabalho contempla uma breve revisão da literatura, empregando os periódicos das bases de dados Scielo, Sciencedirect e ACS, sobre os métodos mais utilizados para síntese do anel 1,2,4-oxadiazólico, destacando suas vantagens e desvantagens. Foi realizada também uma pesquisa sobre as principais funções deste grupamento, sua ação no tratamento de doenças, os testes realizados para a confirmação das ações farmacológicas e os resultados obtidos.Palavras-chave: oxadiazolas; síntese; farmacologia. ABSTRACT:This work includes a brief literature review, using the periodicals of the Scielo, Sciencedirect and ACS databases, about the most used methods for the synthesis of 1,2,4-oxadiazole ring, highlighting their advantages and disadvantages. It was also done a search in the literature about the main functions of this group, its action in the treatment of diseases, the tests made for the confirmation of the pharmacological actions and the results obtained.

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Organocatalytic Oxidative Cyclization of Amidoximes for the Synthesis of 1,2,4‐Oxadiazolines

2018

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Organocatalytic synthesis of bi‐ and tricyclic fused 1,2,4‐oxadiazolines is reported. The reaction proceeds through oxidative cyclization of the corresponding amidoxime using 2,4,6‐tris(4‐fluorophenyl)pyrylium tetrafluoroborate (T(p‐F)PPT) as the organocatalyst, and molecular oxygen as the green oxidant. During the transformation, T(p‐F)PPT acts as both the electrophilic catalyst and photocatalyst, and the reaction is promoted by irradiation with visible light. The method introduced herein offers a straightforward route to the preparation of 1,2,4‐oxadiazolines with different functionalities, and is highly atom economical.magnified image

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New GABA-modulating 1,2,4-oxadiazole derivatives and their anticonvulsant activity

Cited by 68 publications

References 17 publications

Synthesis, Molecular Structure Optimization, and Cytotoxicity Assay of a Novel 2-Acetyl-3-amino-5-[(2-oxopropyl)sulfanyl]-4-cyanothiophene

Synthesis, Molecular Structure Optimization, and Cytotoxicity Assay of a Novel 2-Acetyl-3-amino-5-[(2-oxopropyl)sulfanyl]-4-cyanothiophene

1,2,4-oxadiazole: A Brief Review from the Literature About the Synthesis and Pharmacological Applications

Organocatalytic Oxidative Cyclization of Amidoximes for the Synthesis of 1,2,4‐Oxadiazolines

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