2349-76-0Relevant academic research and scientific papers
Role of Noncovalent Sulfur···Oxygen Interactions in Phenoxyl Radical Stabilization: Synthesis of Super Tocopherol-like Antioxidants
Menichetti, Stefano,Amorati, Riccardo,Meoni, Valentina,Tofani, Lorenzo,Caminati, Gabriella,Viglianisi, Caterina
, p. 5464 - 5467 (2016)
Noncovalent sulfur···oxygen interactions can increase the stability of chalcogen ortho-substituted phenoxyl radicals. This effect contributes to transforming the 7-hydroxybenzo[b]thiophene moiety in a privileged structural motif to enhance the activity of
The synthesis and evaluation of thymoquinone analogues as anti-ovarian cancer and antimalarial agents
Johnson-Ajinwo, Okiemute Rosa,Ullah, Imran,Mbye, Haddijatou,Richardson, Alan,Horrocks, Paul,Li, Wen-Wu
supporting information, p. 1219 - 1222 (2018/03/12)
Thymoquinone (TQ), 2-isopropyl-5-methyl-1,4-benzoquinone, a natural product isolated from Nigella sativa L., has previously been demonstrated to exhibit antiproliferative activity in vitro against a range of cancers as well as the human malarial parasite Plasmodium falciparum. We describe here the synthesis of a series of analogues of TQ that explore the potential for nitrogen-substitution to this scaffold, or reduction to a hydroquinone scaffold, in increasing the potency of this antiproliferative activity against ovarian cancer cell lines and P. falciparum. In addition, alkyl or halogen-substituted analogues were commercially sourced and tested in parallel. Several TQ analogues with improved potency against ovarian cancer cells and P. falciparum were found, although this increase is suggested to be moderate. Key aspects of the structure activity relationship that could be further explored are highlighted.
Model studies of topaquinone-dependent amine oxidases. 1. Oxidation of benzylamine by topaquinone analogs
Mure, Minae,Klinman, Judith P.
, p. 8698 - 8706 (2007/10/02)
The aerobic oxidation of benzylamine by model compounds of topaquinone, the active site organic cofactor in copper-containing amine oxidases, was studied in order to elucidate the chemical function of the cofactor in substrate oxidation. In this study, topaquinone hydantoin (1(ox)) and a series of 2-hydroxy-5-alkyl-1,4-benzoquinones which differ in the bulk of their alkyl substituent (5, 6, 7, and 8) were employed as model compounds of the cofactor. The p-quinones (9, 10, 11, and 12) and the o-quinone (13 and 14) were prepared in order to compare them to the topaquinone analogs. Benzylamine was oxidized by the topaquinone analogs (1(ox), 5, 6, 7, and 8) to yield N-benzylidenebenzylamine (PhCH = NCH2Ph) as a sole product in acetonitrile at room temperature. The quinones bearing a bulky substituent (1(ox), 5, and 6) were found to be more efficient catalysts than those bearing a small primary alkyl group (7 and 8). In the latter case, the dimers (16 and 17) of the substrate Schiff base intermediates (15, R = methyl, ethyl) were isolated. The p-quinones (9, 10, 11, and 12) were catalytically inactive. The o-quinones (13 and 14) had detectable catalytic activity at room temperature. In anaerobic reactions of the o-quinones (13 and 14) with benzylamine, quantitative formation of the product (PhCH = NCH2Ph) was observed. For both o-quinones, products and intermediates which support a transamination mechanism were identified by 1H NMR spectroscopy. The order of reactivity of quinones (5 > 14 > 13) reflects their redox potentials, such that regeneration of quinone may be rate-determining with o-quinones. These results demonstrate a substantial role of the 2-hydroxyl group of the topaquinone in preventing the formation of Michael adducts with substrate amine and in facilitating the reoxidation of aminoresorcinol intermediates.
