Disease relevance of NSC51296

• In addition, butenolide 28 efficiently decreased tumor formation induced by Moloney murine sarcoma virus (MSV) in NMRI mice while significantly increasing the survival time of MSV-infected mice [1].
• 2-Buten-4-olide (2-B4O) inhibits experimental allergic encephalomyelitis (EAE) in Lewis rats [2].
• The order of toxicity of individual toxins was T 2 greater than DAS greater than FX greater than Bd [3].

Psychiatry related information on NSC51296

• 2-buten 4 olide affects feeding behavior of rhesus monkey [4].

High impact information on NSC51296

• Two of the enzymes, FPG and NEIL1 known to cleave normal abasic sites (1) by effecting beta,delta-elimination form cross-links to the butenolide lesion (4) [5].
• It was also discovered that both the butenolide and ethylene glycol subunits play essential roles in the cytotoxicities against tumor cell lines, while the 10-substituted hydroxy group and the absolute configuration of methyl group at the butenolide moiety are less important for their activity [6].
• Butenolide endothelin antagonists with improved aqueous solubility [7].
• Further structural modifications around the butenolide ring led directly to the subnanomolar ETA selective antagonist PD156707, IC50's = 0.3 (ET(A)) and 780 nM (ET(B)) [8].
• In this report we will describe the detailed structure-activity relationship (SAR) studies that led to the discovery of a potent series of butenolide ETA selective antagonists [8].

Biological context of NSC51296

• These results indicate that the novel synthesized retinoidal butenolide KYN-54 inhibits oral carcinogenesis initiated with 4-NQO and such inhibition may be related to suppression of cell proliferation [9].
• Dimerization of the resulting butenolide 11 is then achieved via alkyne metathesis using (tBuO)(3)W&tbd1;CCMe(3) as the catalyst [10].
• A new strategy for the synthesis of bicyclic gamma-alkylidenebutenolides, butenolide-medium ring ether hybrids, is reported which involves Me(3)SiOTf-catalyzed cyclization of 1, 3-bis(trimethylsilyloxy)-1,3-butadienes with oxalyl chloride, Mitsunobu reaction, and subsequent ring-closing metathesis [11].
• Dimerization of butenolide structures. A biomimetic approach to the dimeric sesquiterpene lactones (+/-)-biatractylolide and (+/-)-biepiasterolide [12].
• Intraperitoneal administration of 2-buten-4-olide in doses of 30 to 100 mg/kg, decreased food intake dose-dependently by reducing meal frequency, meal size and eating rate, and prolonging meal duration, latency to eat the first meal after injection and post-prandial intermeal intervals [13].

Anatomical context of NSC51296

• 2-Buten-4-olide (2-B4O), which inhibits the activity of the vagus nerve through the central nervous system, prevented 2-DG-induced uptake of [3H]choline and subsequent synthesis of [3H]ACh, as well as the increase in secretion of gastric acid [14].
• Induction of Fos-like immunoreactivity in the rat hypothalamus by an endogenous feeding suppressant (2-buten-4-olide) [15].
• Induction of Fos-like immunoreactivity in the lower brainstem and the spinal cord of the rat by intraperitoneal administration of an endogenous satiety substance, 2-buten-4-olide [16].
• Effect of an endogenous satiety substance, 2-buten-4-olide, on gastric acid secretion and experimental ulceration in rats [17].
• Mild to moderate degeneration of fibrocytes and cellular infiltration were found in the corium of skin treated with FX, Bd, DAS and T 2 [3].

Associations of NSC51296 with other chemical compounds

• Chemoprevention of azoxymethane-induced intestinal carcinogenesis by a novel synthesized retinoidal butenolide, 5-hydroxy-4-(2-phenyl-(E)-ethenyl)-2(5H)-furanone, in rats [18].
• The modifying effect of dietary exposure of a newly synthesized retinoidal butenolide, 5-hydroxy-4-(2-phenyl-(E)-ethenyl)-2(5H)-furanone (KYN-54) during the initiation and post-initiation phases of oral carcinogenesis initiated with 4-nitroquinoline-1-oxide (4-NQO) was investigated in male F344 rats [9].
• X-ray crystallographic analysis of the closed butenolide form of PD156707 shows the benzylic group located on the same side of the butenolide ring as the gamma-hydroxyl and the remaining two phenyl groups on the butenolide ring essentially orthogonal to the butenolide ring [8].
• Capillary- and packed-column supercritical fluid chromatography has been used for the separation of Fusarium mycotoxins of various structure types such as the trichothecenes including deoxynivalenol and its acetylated derivatives and T-2 toxin, as well as butenolide, culmorin, sambucinol and zearalenone [19].
• An effect of 2-buten-4-olide (2-B4O), an endogenous satiety substance, on hypothalamic dopamine neurons of rats was studied by double-label immunohistochemistry for c-Fos and tyrosine hydroxylase (TH) [20].

Gene context of NSC51296

• 1 We have synthesized a new low molecular weight, non-peptide radioligand, [125I]-PD164333, an analogue of the orally active butenolide antagonists of the endothelin ETA receptor [21].
• The short chain sugar acid, 2-buten-4-olide, activates oxytocin-secreting neurons but not arginine vasopressin-secreting neurons in the hypothalamus of rats [22].
• Modification of the substituents around the butenolide ring has led to compounds with differing selectivity for human ETA and ETB receptors [23].
• The butenolide termini are attached to the ACD, BCE, or BCD intermediates by means of a Sonogashira coupling [24].
• Selective inhibition of separated forms of cyclic nucleotide phosphodiesterase from rat heart by some cardio- or vaso-active butenolide derivatives [25].

Analytical, diagnostic and therapeutic context of NSC51296

• Induction of Fos in neurons by intraperitoneal injection of 2-buten-4-olide (2-B40), an endogenous satiety substance, was studied immunohistochemically in the brainstem and spinal cord of the rat [16].
• 2-Buten-4-olide (2-B4O) inhibits type II collagen-induced arthritis in Lewis rats [26].
• Central action of endogenous sugar acid (2-buten-4-olide): comparison with local anesthesia in hypothalamus [27].
• Quantitative gas chromatography (GC) analysis indicated that the addition of epicatechin to glucose or fructose/glycine model systems significantly reduced the generation of hydroxyacetone, 2-methylpyrazine, 2,3,5-trimethylpyrazine, furfural, 2-acetylfuran, 5-methylfurfural, 2(5H)-furanone, 2-acetylpyrrole, and furfuryl alcohol [28].
• We await data from clinical trials to confirm the therapeutic potential of the ETA-selective butenolide antagonists in man [29].

References