81580-97-4Relevant academic research and scientific papers
Synthesis, biological evaluation and docking studies of trans-stilbene methylthio derivatives as cytochromes P450 family 1 inhibitors
Wierzchowski, Marcin,Dutkiewicz, Zbigniew,Gielara-Korzańska, Agnieszka,Korzański, Artur,Teubert, Anna,Te?yk, Artur,Stefański, Tomasz,Baer-Dubowska, Wanda,Mikstacka, Renata
, p. 1226 - 1236 (2017)
Cytochromes P450 family 1 (CYP1) are responsible for the metabolism of procarcinogens, for example polycyclic aromatic hydrocarbons and aromatic and heterocyclic amines. The inhibition of CYP1 activity is examined in terms of chemoprevention and cancer chemotherapy. We designed and synthesized a series of trans-stilbene derivatives possessing a combination of methoxy and methylthio functional groups attached in different positions to the trans-stilbene skeleton. We determined the effects of synthesized compounds on the activities of human recombinant CYP1A1, CYP1A2 and CYP1B1 and, to explain the variation of inhibitory potency of methoxystilbene derivatives and their methylthio analogues, we employed computational analysis. The compounds were docked to CYP1A1, CYP1A2 and CYP1B1 binding sites with the use of Accelrys Discovery Studio 4.0 by the CDOCKER procedure. For CYP1A2 and CYP1B1, values of scoring functions correlated well with inhibitory potency of stilbene derivatives. All compounds were relatively poor inhibitors of CYP1A2 that possess the most narrow and flat enzyme cavity among CYP1s. For the most active CYP1A1 inhibitor, 2-methoxy-4′-methylthio-trans-stilbene, a high number of molecular interactions was observed, although the interaction energies were not distinctive.
Addition Reactions of Benzothiophen. Part 3. Addition and Ring-opening Reactions with Phenolic Ethers
Clark, Peter David,Ewing, David F.,Kerrigan, Frank,Scrowston, Richard M.
, p. 615 - 622 (2007/10/02)
In the presence of aluminium chloride, anisole, phenetole, diphenyl ether, and (methylthio)benzene are added rapidly across the 2,3-bond in benzothiophen to give, inter alia, a mixture of 2- and 3-(p-substituted aryl)-2,3-dihydrobenzothiophens (3) and (4).Contrary to expectation, the 2-isomer predominates in all cases, and the addition is irreversible.Reaction with anisole also leads to a novel ring-opened product, viz. (E)-4-methoxy-2'-methylthiostilbene (9a), which was synthesised unambigiuously.It is believed that benzothiophen is S-methylated by PhOMe-AlCl3 in a 'push-pull' reaction, and that the resulting positive charge is delocalised into the ring, thus allowing the 2-position to participate in electrophilic attack on a second molecule of anisole.The resulting quadrivalent sulphur intermediate achieves stabilisation by means of a rapid ring-opening reaction.Other aromatic methyl ethers give analogous products, but phenetole diphenyl ether, and (methylthio)benzene do not promote ring-opening.The ring-opening reaction is aided by the addition of MeBr- or EtBr-AlCl3; even phenetole will then undergo ring-opening.Under these conditions the S-alkyl group in the ring-opened product comes from the starting ether, and not from the added MeBr or EtBr.
