Dataset Information

TFA-catalyzed Q-Tube Reactor-Assisted Strategy for the Synthesis of Pyrido[1,2-b][1,2,4]triazine and Pyrido[1',2':2,3][1,2,4]triazino[5,6-b]indole Derivatives.

ABSTRACT: An efficient high-pressure-assisted trifluoroacetic acid-catalyzed protocol for synthesizing unreported novel pyrido[1,2-b][1,2,4]triazine and pyrido[1',2':2,3][1,2,4]triazino[5,6-b]indole derivatives has been established. This strategy includes the condensation reactions of various 1-amino-2-imino-4-arylpyridine-3-carbonitrile derivatives with indoline-2,3-dione (isatin) derivatives and α-keto acids such as pyruvic acid and phenylglyoxylic acid. This strategy includes utilizing the Q-tube reactor as an efficient and safe tool to conduct these reactions under high-pressure conditions. In addition, trifluoroacetic acid was used to induce this transformation. In this research, conducting the targeted reactions under high pressure using the Q-tube reactor was found to be superb in comparison to that under the traditional refluxing conditions. X-ray single-crystal analysis was utilized in this study to authenticate the structure of the synthesized products.

SUBMITTER: Ibrahim HM

PROVIDER: S-EPMC8223412 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:2-Amino-9H-pyrido[2,3-b]indole (A?C) is a carcinogenic heterocyclic aromatic amine (HAA) that arises in tobacco smoke. UDP-glucuronosyltransferases (UGTs) are important enzymes that detoxicate many procarcinogens, including HAAs. UGTs compete with P450 enzymes, which bioactivate HAAs by N-hydroxylation of the exocyclic amine group; the resultant N-hydroxy-HAA metabolites form covalent adducts with DNA. We have characterized the UGT-catalyzed metabolic products of A?C and the genotoxic metabolite 2-hydroxyamino-9H-pyrido[2,3-b]indole (HONH-A?C) formed with human liver microsomes, recombinant human UGT isoforms, and human hepatocytes. The structures of the metabolites were elucidated by (1)H NMR and mass spectrometry. A?C and HONH-A?C underwent glucuronidation by UGTs to form, respectively, N(2)-(?-D-glucosidurony1)-2-amino-9H-pyrido[2,3-b]indole (A?C-N(2)-Gl) and N(2)-(?-D-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (A?C-HON(2)-Gl). HONH-A?C also underwent glucuronidation to form a novel O-linked glucuronide conjugate, O-(?-D-glucosidurony1)-2-hydroxyamino-9H-pyrido[2,3-b]indole (A?C-HN(2)-O-Gl). A?C-HN(2)-O-Gl is a biologically reactive metabolite and binds to calf thymus DNA (pH 5.0 or 7.0) to form the N-(deoxyguanosin-8-yl)-A?C adduct at 20-50-fold higher levels than the adduct levels formed with HONH-A?C. Major UGT isoforms were examined for their capacity to metabolize A?C and HONH-A?C. UGT1A4 was the most catalytically efficient enzyme (V(max)/K(m)) at forming A?C-N(2)-Gl (0.67 ?l·min(-1)·mg of protein(-1)), and UGT1A9 was most catalytically efficient at forming A?C-HN-O-Gl (77.1 ?l·min(-1)·mg of protein(-1)), whereas UGT1A1 was most efficient at forming A?C-HON(2)-Gl (5.0 ?l·min(-1)·mg of protein(-1)). Human hepatocytes produced A?C-N(2)-Gl and A?C-HN(2)-O-Gl in abundant quantities, but A?C-HON(2)-Gl was a minor product. Thus, UGTs, usually important enzymes in the detoxication of many procarcinogens, serve as a mechanism of bioactivation of HONH-A?C.

Dataset Information

TFA-catalyzed Q-Tube Reactor-Assisted Strategy for the Synthesis of Pyrido[1,2-b][1,2,4]triazine and Pyrido[1',2':2,3][1,2,4]triazino[5,6-b]indole Derivatives.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure