178557-13-6Relevant articles and documents
2C-B-fly-NBOMe metabolites in rat urine, human liver microsomes and c. Elegans: Confirmation with synthesized analytical standards
?e?ková, Hedvika,?íchová, Klára,?uláková, Anna,Hájková, Kate?ina,Jurásek, Bronislav,Kucha?, Martin,Leonhardt, Tereza,Nykodemová, Jitka,Pálení?ek, Tomá?,Palivec, Petr,Rimpelová, Silvie
, (2021/11/30)
Compounds from the N-benzylphenethylamine (NBPEA) class of novel psychoactive substances are being increasingly utilized in neurobiological and clinical research, as diagnostic tools, or for recreational purposes. To understand the pharmacology, safety, or potential toxicity of these substances, elucidating their metabolic fate is therefore of the utmost interest. Several studies on NBPEA metabolism have emerged, but scarce information about substances with a tetrahydrobenzodifuran (“Fly”) moiety is available. Here, we investigated the metabolism of 2-(8-bromo-2,3,6,7-tetrahydrobenzo[1,2-b:4,5-b’]difuran-4-yl)-N-(2-methoxybenzyl)ethan-1-amine (2C-B-Fly-NBOMe) in three different systems: isolated human liver microsomes, Cunninghamella elegans mycelium, and in rats in vivo. Phase I and II metabolites of 2C-B-Fly-NBOMe were first detected in an untargeted screening and identified by liquid chromatography–tandem mass spectrometry (LC– MS/MS). Several hypothesized metabolites were then synthesized as reference standards; knowledge of their fragmentation patterns was utilized for confirmation or tentative identification of isomers. Altogether, thirty-five phase I and nine phase II 2C-B-Fly-NBOMe metabolites were detected. Major detected metabolic pathways were mono-and poly-hydroxylation, O-demethylation, oxidative debromination, and to a lesser extent also N-demethoxybenzylation, followed by glucuronidation and/or N-acetylation. Differences were observed for the three used media. The highest number of metabolites and at highest concentration were found in human liver microsomes. In vivo metabolites detected from rat urine included two poly-hydroxylated metabolites found only in this media. Mycelium matrix contained several dehydrogenated, N-oxygenated, and dibrominated metabolites.
Synthesis and cytotoxic activity of novel tetrahydrobenzodifuran–imidazolium salt derivatives
Zhang, Chao-Bo,Liu, Yang,Liu, Zheng-Fen,Duan, Sheng-Zu,Li, Min-Yan,Chen, Wen,Li, Yan,Zhang, Hong-Bin,Yang, Xiao-Dong
, p. 1808 - 1814 (2017/04/04)
The synthesis of a series of novel 4-substituted 2,3,6,7-tetrahydrobenzo [1,2-b;4,5-b′]difuran–1H-imidazolium salts is presented. The biological properties of the compounds were evaluated in vitro against a panel of human tumor cell lines. Results suggest that the 5,6-dimethyl-benzimidazole or 2-methyl-benzimidazole ring, and substitution of the imidazolyl-3-position with a 2-naphthylmethyl substituent or 2-naphthylacyl substituent, were important to the cytotoxic activity. Notably, 3-(2-Naphthylmethyl)-1-((2,3,6,7-tetrahydrobenzo[1,2-b;4,5-b′]difuran-4-yl)methyl)-1H-5,6-dimethyl-benzimidazol-3-ium bromide (42) was found to be the most potent derivative against five human tumor cell lines with IC50 values of 1.06–4.34?μM and more selective towards SMMC-7721, A549 and SW480 cell lines. 3-(2-Naphthylacyl)-1-((2,3,6,7-tetrahydrobenzo[1,2-b;4,5-b′]difuran-4-yl)methyl)-1H-2-methyl-benzimidazol-3-ium bromide (37) showed higher selectivity to SMMC-7721 and MCF-7 cell lines with IC50 values 2.7-fold and 8.4-fold lower than DDP. Study regarding to the antitumor mechanism of action showed that compound 37 could induce cell cycle G1 phase arrest and apoptosis in SMMC-7721 cells.
