The preparation of ester heterocycles mostly uses heteroatoms as nucleophilic sites, which are achieved by intramolecular substitution or addition reactions. Compound: 5-Methylfuran-2(3H)-one( cas:591-12-8 ) is researched.SDS of cas: 591-12-8.Shangula, S.; Noori, M.; Ahmad, I.; Margison, G. P.; Liu, Y.; Siahmansur, T.; Soran, H.; Povey, A. C. published the article 《PON1 increases cellular DNA damage by lactone substrates》 about this compound( cas:591-12-8 ) in Archives of Toxicology. Keywords: HepG2 cell PON1 DNA damage lactone; DNA damage; Lactones; PON1. Let’s learn more about this compound (cas:591-12-8).
Paraoxonase 1 (PON1) is a high-d. lipoprotein (HDL)-associated enzyme that by hydrolyzing exogenous and endogenous substrates can provide protection against substrate induced toxicity. To investigate the extent to which PON1 provides protection against lactone induced DNA damage, DNA damage was measured in HepG2 cells using the neutral Comet assay following lactone treatment in the presence and absence of exogenous recombinant PON1 (rPON1). Low dose lactones (10 mM) caused little or no damage while high doses (100 mM) induced DNA damage in the following order of potency: α-angelica lactone > γ-butyrolactone > γ-hexalactone > γ-heptalactone > γ-octaclactone >γ-furanone > γ-valerolactone > γ-decalactone. Co-incubation of 100 mM lactone with rPON1, resulted in almost all cells showing extensive DNA damage, particularly with those lactones that decreased rPON1 activity by > 25%. DNA damage induced by a 1 h co-treatment with 10 mM α-angelica lactone and rPON1 was reduced when cells when incubated for a further 4 h in fresh medium suggesting break formation was due to induced DNA damage rather than apoptosis. These results suggest that in addition to its well-recognized detoxification effects, PON1 can increase genotoxicity potentially by hydrolyzing certain lactones to reactive intermediates that increase DNA damage via the formation of DNA adducts.
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Reference:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia