41245-48-1Relevant academic research and scientific papers
Design, synthesis, and biological testing of novel naphthoquinones as substrate-based inhibitors of the quinol/fumarate reductase from Wolinella succinogenes
Nasiri, Hamid Reza,Madej, M. Gregor,Panisch, Robin,Lafontaine, Michael,Bats, Jan W.,Lancaster, C. Roy D.,Schwalbe, Harald
, p. 9530 - 9541 (2014/01/06)
Novel naphthoquinones were designed, synthesized, and tested as substrate-based inhibitors against the membrane-embedded protein quinol/fumarate reductase (QFR) from Wolinella succinogenes, a target closely related to QFRs from the human pathogens Helicobacter pylori and Campylobacter jejuni. For a better understanding of the hitherto structurally unexplored substrate binding pocket, a structure-activity relationship (SAR) study was carried out. Analogues of lawsone (2-hydroxy-1,4-naphthoquinone 3a) were synthesized that vary in length and size of the alkyl side chains (3b-k). A combined study on the prototropic tautomerism of 2-hydroxy-1,4-naphthoquinones series indicated that the 1,4-tautomer is the more stable and biologically relevant isomer and that the presence of the hydroxyl group is crucial for inhibition. Furthermore, 2-bromine-1,4-naphthoquinone (4a-c) and 2-methoxy-1,4-naphthoquinone (5a-b) series were also discovered as novel and potent inhibitors. Compounds 4a and 4b showed IC50 values in low micromolar range in the primary assay and no activity in the counter DT-diaphorase assay.
Synthesis of 2,3-Dialkyl-6,7-dichloro- and 2,3-Dialkyl-6,7-dibromo-1,4-naphthoquinones
Ashnagar, Alamdar,Bruce, J. Malcolm,Lloyd-Williams, Paul
, p. 559 - 562 (2007/10/02)
Thermal treatment of 1,4-benzoquinone and its 2-methyl and 2,3-dimethyl homologues with 3,4-dichlorothiophene 1,1-dioxide followed by oxidation affords the corresponding 6,7-dichloro-1,4-naphthoquinones; the parent compound and its 2-methyl homologue can be alkylated at the free quinonoid positions using the alkanoic acid-persulphate-silver ion system.Nitration of 2,3-dibromonaphthalene yields 2,3-dibromo-5-nitronaphthalene, which via sequential reduction, diazotisation, hydrolysis, and oxidation with Fermy's salt gives 6,7-dibromo-1,4-naphthoquinone, which can be similarly alkylated.
