The Synthesis of N‐Acyl‐2‐hydroxymethyl Aziridines of Biological Interest.

Medjahed, W.; Zatla, Amina Tabet; Mulengi, Joseph Kajima; Ahmed, Fátima; Merzouk, Hafida

doi:10.1002/chin.200419095

Cited by 3 publications

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“…Afin de contribuer à la mise en évidence de l'intérêt et de l'importance de l'utilisation des aziridines au cours de l'immunothérapie, de nouvelles aziridines ont été synthétisées, au niveau du laboratoire COSNA (Chimie organique, substances naturelles et analyses) de la faculté des Sciences (Université de Tlemcen), à partir d'acides aminés [12]. Nous avons dé-montré leurs effets immunomodulateurs, la 2-hydroxy-méthyl-1 (N-phtaloyltryptophyl) aziridine étant la plus immunostimulante [13,14].…”

Section: Discussionunclassified

“…Les réactions chimiques utilisées pour la préparation de cette aziridine à partir du tryptophane ont été publiées et décrites précédemment [12]. La structure chimique de l'aziridine testée est donnée dans la figure 1.…”

Section: Matériel Et Animauxunclassified

“…Vu l'importance des propriétés biologiques des aziridines, de nouvelles voies de synthèse, simples et efficaces, sont de plus en plus recherchées. Afin d'explorer de nouvelles aziridines à activité biologique, nous avons synthétisé des aziridines à partir d'aminoacyl azides protégés selon un mécanisme pré-cédemment décrit [12]. Nous avons mis en évidence le caractère imunomodulateur de ces aziridines dont certaines sont immunostimulantes et d'autres immunosuppressives [13,14].…”

Section: Introductionunclassified

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Évaluation de la toxicité aiguë de la 2-hydroxy-méthyl-1 (N-phtaloyltryptophyl) aziridine chez le rat Wistar

et al. 2010

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Résumé -Objectifs : Les aziridines, molécules alkylantes à l'ADN, possèdent une grande activité anticancéreuse et antibiotique et modulent le système immunitaire. Une nouvelle aziridine, la 2-hydroxy-méthyl-1 (N-phtaloyltryptophyl) aziridine, a été synthétisée dans notre laboratoire. Cependant, sa toxicité n'est pas connue. L'objectif de ce travail est de déterminer la toxicité aiguë de cette aziridine chez le rat Wistar. Matériel et Méthodes : Cinq lots de rats Wistar mâles reçoivent une injection intra péritonéale de 9,35 mg/kg, 37,4 mg/kg, 93,5 mg/kg, 140,25 mg/kg, 187 mg/kg d'aziridine, et sont observés pendant 14 jours. Les mortalités, les modifications du comportement, du poids, et les variations de l'ingestion de nourriture et d'eau, du volume des urines et du poids des fèces sont notées. À la fin de l'expérimentation, les rats recevant la dose sans effet toxique observable (NOAEL) sont sacrifiés, les organes et le sang sont prélevés. Les paramètres hématologiques et biochimiques sont dosés. Résultats : Les résultats montrent que la DL 50 de l'aziridine testée est de 104,71 mg/kg. L'injection de la dose d'aziridine à 9,35 mg/kg (NOAEL) ne provoque pas de mortalité, ni de variations du poids corporel, de la nourriture et l'eau consommés et des excrétas. De plus à cette dose, les taux de globules rouges et blancs et d'hémoglobine ainsi que les paramètres biochimiques (glucose, cholestérol, triglycérides, urée, créatinine, bilirubine, protéines totales, transaminases) et les poids des organes (foie, rein, rate, pancréas, coeur, muscle, et cerceau) ne sont pas affectés. Conclusion : La 2-hydroxy-méthyl-1 (N-phtaloyltryptophyl) aziridine pourrait être éventuellement proposée pour des essais cliniques après avoir procédé à toutes les études toxicologiques pré-requises à ces essais. Mots clés : Aziridine, rat, toxicité aiguëAbstract -Objective: Aziridines, DNA-binding drugs, display potent anticancer and antibiotic activities and modulate the immune system. A new aziridine, 2-hydroxy-méthyl-1 (N-phtaloyltryptophyl) aziridine, was synthesized in our laboratory; however, its toxicity is not known. The aim of this work is to determine the acute toxicity of this aziridine in Wistar rat. Material and Methods: Five groups of male wistar rats were treated with 9.35 mg/kg, 37.4 mg/kg, 93.5 mg/kg, 140.25 mg/kg and 187 mg/kg of the aziridine, and were observed for 14 days. The mortality, comportmental and weight modifications, food and water consumption, and urine volume and feces weight were recorded. At day 14, rats treated with the dose without observable toxic effects (NOAEL) were killed, and organs and blood were taken. Hematological and biochemical parameters were investigated. Results: Our results showed that the DL 50 of the aziridine tested is 104.71 mg/kg. The administration of this drug at 9.35 mg/kg (NOAEL) had no effects on mortality, body weight, food and water consumed, or excreta. Erythrocyte and leukocyte counts, hemoglobin concentration, and biochemical parameters (glucose, cholesterol, triglycerides, ur...

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Section: Discussionunclassified

Section: Matériel Et Animauxunclassified

Section: Introductionunclassified

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Évaluation de la toxicité aiguë de la 2-hydroxy-méthyl-1 (N-phtaloyltryptophyl) aziridine chez le rat Wistar

et al. 2010

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“…Reaction of 9 and ethyl bromoacetate in benzene in the presence of NaH and subsequent hydrolysis of ester 10 by 4 N HCl in dioxane gave the acid 11 in overall 40% yield. All the other acids were obtained commercially or prepared by the following methods: The N , N ‐phthaloyl‐amino acids were obtained according to previously described procedure (19,20). The N ‐saccharinyl acetic acid was prepared from sodium saccharin and chloroacetic acid (21).…”

Section: Methodsmentioning

confidence: 99%

Design, Biologic Evaluation, and SAR of Novel Pseudo‐peptide Incorporating Benzheterocycles as HIV‐1 Protease Inhibitors

Zhang

Yao

et al. 2010

Chem Biol Drug Des

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A series of novel HIV‐1 protease inhibitors based on the (hydroxyethylamino)‐sulfonamide isostere incorporating substituted phenyls and benzheterocycle derivatives bearing rich hydrogen bonding acceptors as P2 ligands were synthesized. Prolonged chain linking the benzhereocycle to the carbonyl group resulted in partial loss of binding affinities. Introduction of a small alkyl substituent with appropriate size to the ‐CH2‐ of P1‐P2 linkage as a side chain resulted in improved inhibitory potency, and in this study, isopropyl was the best side chain. Replacement of the isobutyl substituent at P1′group with phenyl substituent decreased the inhibitory potency. One of the most potent inhibitor, compound 23 showing high affinity to HIV‐1 protease with an IC50 value of 5 nm, also exhibited good anti‐SIV activity (EC50 = 0.8 μm) with low toxicity (TC50 > 100 μm). The flexible docking of inhibitor 23 to HIV‐1 protease active site rationalized the interactions with protease.

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“…Taking into account the various biological activities of triazoles, isoxazolines, isoxazoles, aziridines, and coumarins cited, respectively, in the literature [30][31][32][33] , it appeared to us interesting to think about the combination of these moieties hoping to access to more biologically effective compounds. In this context and as a continuation of our previous work on the synthesis of new fused 4-methylumbelliferone scaffolds 34 , we report here the synthesis of a diverse series of novel triazoles, isoxazoles, isoxazolines, and aziridines linked to 4-methylumbelliferone through [3 + 2] cycloaddition in the side chain.…”

Section: Introductionmentioning

confidence: 99%

Design and synthesis of antimicrobial, anticoagulant, and anticholinesterase hybrid molecules from 4-methylumbelliferone

Zayane

Rahmouni

Daami‐Remadi

et al. 2016

Journal of Enzyme Inhibition and Medicinal Chemistry

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We designed and synthesized new series of diverse triazoles, isoxazoles, isoxazolines, and aziridines linked 4-methylumbelliferone 1 using intermolecular 1,3-dipolar cycloaddition reactions. Structures of these compounds were established on the basis of 1 H NMR, 13 C NMR, and ESI-HRMS. All prepared compounds were evaluated for their antimicrobial, anticoagulant, and anticholinesterase activities. Interestingly, among the tested molecules, some of the analogs displayed better activities than the parent 4-methylumbelliferone 1 such as 6a and 6d for their antifungal properties. Moreover, compounds 4, 5, 6, and 7 showed the importance of the added fragments to 4-methylumbelliferone 1 via the linker methylene to have good activity.

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The Synthesis of N‐Acyl‐2‐hydroxymethyl Aziridines of Biological Interest.

Abstract: Protected acylazides (I) and triphenylphosphine generate iminophosphoranes which are trapped by the sodium salt (II) of glycidol to afford the title compounds (III). These can be considered as novel dipeptide isostere precursors. -(MEDJAHED, W.; ZATLA, A. T.; MULENGI*,

Cited by 3 publications

References 1 publication

Évaluation de la toxicité aiguë de la 2-hydroxy-méthyl-1 (N-phtaloyltryptophyl) aziridine chez le rat Wistar

Évaluation de la toxicité aiguë de la 2-hydroxy-méthyl-1 (N-phtaloyltryptophyl) aziridine chez le rat Wistar

Design, Biologic Evaluation, and SAR of Novel Pseudo‐peptide Incorporating Benzheterocycles as HIV‐1 Protease Inhibitors

Design and synthesis of antimicrobial, anticoagulant, and anticholinesterase hybrid molecules from 4-methylumbelliferone

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