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Results for “Aziridines”

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At least 19 recordsLinked to original sources
PubMed2026

Unveiling Aziridine-Containing Natural Products by Genomic and Spectroscopic Approaches.

Aziridine-containing natural products are prized for their potent bioactivities, yet their scarcity and poorly understood biosynthesis have limited systematic exploration. Here, we address this by integrating genome mining with a 1H-13C coupled HSQC metabolomic approach that exploits the distinctive NMR signatures of aziridines, enabling their direct detection from complex extracts. This strategy unveiled the desertolides, the first macrolides incorporating a rare terminal 2-methyl-aziridine-2-carboxylate moiety. Genetic and isotopic studies identified a dedicated biosynthetic subcluster (desA-desN) that assembles and installs this unit from glutamate, and heterologous expression confirmed the self-sufficiency of this subcluster. Direct MS evidence reveals the aziridine moiety covalently bound to the active-site Cys113 of DesN, establishing this KAS III homolog as the first dedicated aziridine-transferase and a promising tool for polyketide engineering. Bioinformatic analysis uncovered over 50 biosynthetic gene clusters, suggesting that this aziridine-associated biosynthetic logic may be more widespread than currently appreciated. This work establishes a tractable platform for the targeted discovery and engineered biosynthesis of aziridine-containing natural products, opening this underexplored pharmacophore to systematic interrogation.

Aziridines↗
PubMed1977

The interaction of 1-(2(diarylmethoxy)ethyl)aziridines with histamine receptors in the longitudinal muscle strip of the guinea pig ileum.

The time course of the onset and decline of histamine antagonism by 1-(2-(diarylmethoxy)ethyl)aziridines, compounds which could be expected to have H1-receptor alkylating properties, was investigated on the longitudinal muscle strip of the guinea pig ileum. Experiments were performed with normal preparations and with muscle strips pretreated with a prostaglandin synthesis inhibitor in order to prevent spontaneous rise of muscle tone. In contrast to the previously reported observation that antihistaminic potency decreased with prolongation of the preincubation time, histamine antagonism by the aziridine compounds remained at a constant level for more than 60 min in the presence of indomethacin. This indicated that the aziridines are not hydrolyzed either directly in solution or after interaction with the tissue since the supposed hydrolysis product had a significantly lower antihistaminic activity. A comparison between 1-(2-diphenylmethoxy)ethyl)aziridine and diphenhydramine showed the former compound to have a slightly more rapid onset and a considerably more rapid decline of histamine receptor blockade. It was concluded that 1-(2-(diarylmethoxy)ethyl)aziridines did not alkylate the histamine H1-receptor in the longitudinal muscle layer of the guinea pig ileum.

Animals↗
PubMedDate not supplied

[Preliminary study of the comparative action of 1 methyl-2 (2 naphtyl) aziridine on kindling effect and on paradoxical sleep (author's transl)].

Methyl-2 (2 Naphtyl) Aziridine (MNA) is a new agent which has been demonstrated to have effects on paradoxical sleep (PS) and on the levels of cerebral noradrenaline (Yamamoto, 1975). It has been tried on a experimental model of epilepsy, the kindling effect, produced in the cat by repetitive stimulation of the amygdala. The results obtained in the cat confirmed blockage of paradoxical sleep (PS) and revealed a marked reduction in the number of stimuli required to produce the effect. The shortening of the time before the first generalised seizure did not seem attributable to privation of paradoxical sleep. The role of cerebral catecholamine reduction, however, is discussed.

Animals↗
PubMed1975

Aziridine.

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Animals↗
PubMed1978

Adrenoceptor blocking agents. 2. 2-(alpha-Hydroxyarylmethyl)-3,3-dimethylaziridines, a new class of selective beta2-adrenoceptor antagonists.

Threo- and erythro-2-(alpha-hydroxybenzyl)-3,3-dimethylaziridines (1a and 1b) and threo-2-[alpha-hydroxy(2-naphthyl)methyl]- and 2-[alpha-hydroxy(3,4-dichlorobenzyl)]-3,3-dimethylaziridines (1d and 1c) have been prepared as conformationally restricted analogues of beta-adrenoceptor blocking agents like dichloroisoproterenol (DCI) and pronethalol. The aziridine analogues 1 except possibly 1c are competitive antagonists of isoproterenol-induced response on a guinea pig tracheal chain preparation and the order of potency is 1d greater than 1a greater than or equal to 1b greater than propranolol greater than 1c. Unlike propranolol, these compounds have no effect on the isoproterenol-induced response on guinea pig auricles and no significant local anesthetic and antiarrhythmic activity. The aziridine analogues 1 represent the first of a new class of selective beta2-adrenoceptor blocking agents.

Adrenergic beta-Antagonists↗
PubMed1978

Platinum complexes as radiosensitizers of hypoxic mammalian cells.

Cis-dichlorodiammineplatinum (II), or cis-PDD, has recently been shown to be a potent radiosensitizer of bacteria, particularly under conditions of acute hypoxia. This study extends this observation to include the radiosensitization of mammalian cell (V-79) by low concentrations of cis-PDD, cis-dichlorobis(aziridine) platinum (II), and the trans-isomer of PDD as measured from survival curve analysis. This radiosensitization was obtained at concentrations of 10 micrometer, 60 micrometer, and 100 micrometer for the cis-PDD, aziridine-platinum, and trans-isomer respectively. The corresponding drug toxicity survival levels were 8, 40 and 50%. Dose modification factors of around 1.3 to 1.4 were observed.

Aziridines↗
PubMed1978

A new methods for the 3'-deoxygenation of butirosins A and B.

An aziridine ring-formation involving the reaction of adjacent amino and alcohol groups with triphenylphosphine, carbon tetrachloride, and triethylamine was applied at the 2' and 3' positions of butirosin A (1a) and B (1b). The amino groups at the 2' position of 1a and 1b were p-methoxybenzylated to increase the nucleophilicity of the nitrogen atom and to avoid the formation of a P-N linkage, and the N-p-methoxybenzyl derivatives were converted into the aziridine derivatives, which were then subjected to hydrogenolysis and removal of the protecting groups to give 3'-deoxybutirosin A (7a) and B (7b), respectively. This new method is compared with the conventional N,O-protecting method that involves several complex steps.

Anti-Bacterial Agents↗
PubMed1976

Studies related to antitumor antibiotics. Part V. Reactions of mitomycin C with DNA examined by ethidium fluorescence assay.

The cytotoxic action of the antitumor antibiotic mitomycin C occurs primarily at the level of DNA. Using highly sensitive fluorescence assays which depend on the enhancement of ethidium fluorescence only when it intercalates duplex regions of DNA, three aspects of mitomycin C action on DNA have been studied: (a) cross-linking events, (b) alkylation without necessarily cross-linking, and (c) strand breakage. Cross-linking of DNA is determined by the return of fluorescence after a heat denaturation step at alkaline pH's. Under these conditions denatured DNA gives no fluorescence. The cross-linking was independently confirmed by S1-endonuclease (EC 3.1.4.-) digestion. At relatively high concentrations of mitomycin the suppression of ethidium fluorescence enhancement was shown not to be due to depurination but rather to alkylation, as a result of losses in potential intercalation sites. A linear relationship exists between binding ratio for mitomycin and loss of fluorescence. The proportional decrease in fluorescence with pH strongly suggests that the alkylation is due to the aziridine moiety of the antibiotic under these conditions. A parallel increase in the rate and overall efficiency of covalent cross-linking of DNA with lower pH suggests that the cross-linking event, to which the primary cytotoxic action has been linked, occurs sequentially with alkylation by aziridine and then by carbamate. Mitomycin C, reduced chemically, was shown to induce single strand cleavage as well as monoaklylation and covalent cross-linking in PM2 covalently closed circular DNA. The inhibition of this cleavage by superoxide dismutase (EC 1.15.1.1) and catalase (EC 1.11.1.6), and by free radical scavengers suggests that the degradation of DNA observed to accompany the cytotoxic action of mitomycin C is largely due to the free radical O2. In contrast to the behavior of the antibiotic streptonigrin, mitomycin C does not inactivate the protective enzymes superoxide dismutase or catalase. Lastly, mitomycin C is able to cross-link DNA in the absence of reduction at pH 4. This is consistent with the postulated cross-linking mechansims.

Animals↗
PubMed1975

Binary ethylenimine as an inactivant for foot-and-mouth disease virus and its application for vaccine production.

Foot-and-mouth disease virus was inactivated with binary ethylenimine formed apart from or directly in the virus suspension by the cyclization of 2-bromoethylamine hydrobromide or 2-chloroethylamine hydrochloride under alkaline conditions. The inactivation rates with binary ethylenimine prepared apart from the virus suspension in dilute sodium hydroxide with either 2-bromoethylamine hydrobromide or 2-chlorethylamine hydrochloride were higher than with pure ethylenimine. When binary ethylenime was prepared directly in the virus suspension only 2-bromoethylamine hydrobromide gave acceptable inactivation rates. The reduced inactivation rates for binary ethylenimine directly prepared in the virus suspension are due to the different cyclization rates of 2-bromoethylamine hydrobromide and 2-chloroethylamine hydrochloride and to the interference of bicarbonate in the cyclization reaction. The complement fixing antigen of foot-and-mouth disease virus was not affected by binary ethylenimine inactivation. Vaccines prepared with foot-and-mouth disease virus inactivated by binary ethylenimine were comparable in their immunogenicity to vaccines prepared with ethylenimine or N-acetylethylenimine used as inactivants. Application of binary ethylenimine in the preparation of foot-and-mouth disease vaccines considerably reduces the potential danger associated with handling pure ethylenimine and other aziridines.

Animals↗
PubMed1978

5-Carboxamido-4-amino-3-isoxazolidone, and asparagine analogue.

trans-Aziridine-2,3-dicarboxylic ester was used to prepare the required beta-chlorohydroxamic acid used in the synthesis of the title compound. The trans configuration of the asparagine analogue was established by hydrogenolysis to erythro-beta-hydroxyasparagine amide. Neither the title compound nor the intermediate aziridinehydroxamic acid (8) showed significant activity against the L1210 and P-388 tumors. The title compound was inactive as an inhibitor of asparagine synthetase from Novikoff hepatoma and did not inhibit the growth of some 25 bacteria and fungi.

Animals↗
PubMed1976

[Coenzym properties of some Ade-1- and Ade-N6-substituted NAD derivatives (author's transl)].

By reaction of NAD with different oxiranes or with aziridine, derivatives of the coenzyme are obtained with substituents in position 1 or on the amino group in position 6 of the adenine ring. While the Ade-1-substituted derivatives show high Km values with different dehydrogenases and are reduced only very slowly by these enzymes, the coenzyme derivatives substituted at the amino group behave very similarly to NAD. Correlations were found between coenzyme efficiency of the compounds and the lipophilic character of their substituents. The results can be interpreted from the structure of the active site of the dehydrogenases investigated.

Coenzymes↗
PubMed1978

Experimental renal papillary necrosis in the rat: the selective vulnerability of medullary structures to injury.

Acute renal papillary necrosis was produced in rats by the administration of ethyleneimine. Low doses resulted in necrosis of interstitial cells, thin limbs of the loops of Henle and vasa recta, while collecting ducts were spared (subtotal renal papillary necrosis). High doses resulted in necrosis of all elements of the papilla (total renal papillary necrosis). Athough the ranges of the doses that produced these two patterns of necrosis overlapped, it is clear that there is a dose dependent selective vulnerability or renal medullary structures to injury by the toxic agent studied.

Animals↗
PubMed1975

The effect of acetylethyleneimine upon a strain of inactivated foot-and-mouth disease virus stored at 4 degrees C.

The presence of either thiosulphate-neutralized or free AEI was shown to degrade inactivated foot-and-mouth disease virus Type O (Hong Kong) antigen during storage at 4 degrees C. Deterioration was evident after 20 weeks of storage and little antigen remained at 36 weeks. Optimum stability was obtained by removing the residual inactivant immediately after inactivation.

Animals↗