- New aryloxy-quinone derivatives with promising activity on Trypanosoma cruzi
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Continuing with a program to develop new quinone derivatives as biologically active compounds, we designed and synthesized a new series of aryloxy-quinones, which were evaluated in vitro against Trypanosoma cruzi in epimastigote form. Chemical modificatio
- Espinosa-Bustos, Christian,Vázquez, Karina,Varela, Javier,Cerecetto, Hugo,Paulino, Margot,Segura, Rodrigo,Pizarro, Jaime,Vera, Brenda,González, Mercedes,Zarate, Ana M.,Salas, Cristian O.
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- Cesium carbonate-mediated reaction of dichloronaphthoquinone derivatives with O-nucleophiles
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A cesium carbonate-mediated reaction of 2,3-dichloronaphthoquinone, 6,7-dichloro-5,8-quinolinedione, and -isoquinolinedione with oxygen nucleophiles has been described.
- Lee, Do-Min,Ko, Ju Hong,Lee, Kee-In
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- Discovery of Novel 2-Aniline-1,4-naphthoquinones as Potential New Drug Treatment for Leber's Hereditary Optic Neuropathy (LHON)
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Leber's hereditary optic neuropathy (LHON) is a rare genetic mitochondrial disease and the primary cause of chronic visual impairment for at least 1 in 10 ?000 individuals in the U.K. Treatment options remain limited, with only a few drug candidates and therapeutic approaches, either approved or in development. Recently, idebenone has been investigated as drug therapy in the treatment of LHON, although evidence for the efficacy of idebenone is limited in the literature. NAD(P)H:quinone oxidoreductase 1 (NQO1) and mitochondrial complex III were identified as the major enzymes involved in idebenone activity. Based on this mode of action, computer-aided techniques and structure-activity relationship (SAR) optimization studies led to the discovery of a series naphthoquinone-related small molecules, with comparable adenosine 5′-triphosphate (ATP) rescue activity to idebenone. Among these, three compounds showed activity in the nanomolar range and one, 2-((4-fluoro-3-(trifluoromethyl)phenyl)amino)-3-(methylthio)naphthalene-1,3-dione (1), demonstrated significantly higher potency ex vivo, and significantly lower cytotoxicity, than idebenone.
- Varricchio, Carmine,Beirne, Kathy,Aeschlimann, Pascale,Heard, Charles,Rozanowska, Malgorzata,Votruba, Marcela,Brancale, Andrea
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p. 13638 - 13655
(2020/11/30)
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- Structure-activity relationships and colorimetric properties of specific probes for the putative cancer biomarker human arylamine N-acetyltransferase 1
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A naphthoquinone inhibitor of human arylamine N-acetyltransferase 1 (hNAT1), a potential cancer biomarker and therapeutic target, has been reported which undergoes a distinctive concomitant color change from red to blue upon binding to the enzyme. Here we describe the use of in silico modeling alongside structure-activity relationship studies to advance the hit compound towards a potential probe to quantify hNAT1 levels in tissues. Derivatives with both a fifty-fold higher potency against hNAT1 and a two-fold greater absorption coefficient compared to the initial hit have been synthesized; these compounds retain specificity for hNAT1 and its murine homologue mNat2 over the isoenzyme hNAT2. A relationship between pKa, inhibitor potency and colorimetric properties has also been uncovered. The high potency of representative examples against hNAT1 in ZR-75-1 cell extracts also paves the way for the development of inhibitors with improved intrinsic sensitivity which could enable detection of hNAT1 in tissue samples and potentially act as tools for elucidating the unknown role hNAT1 plays in ER+ breast cancer; this could in turn lead to a therapeutic use for such inhibitors.
- Egleton, James E.,Thinnes, Cyrille C.,Seden, Peter T.,Laurieri, Nicola,Lee, Siu Po,Hadavizadeh, Kate S.,Measures, Angelina R.,Jones, Alan M.,Thompson, Sam,Varney, Amy,Wynne, Graham M.,Ryan, Ali,Sim, Edith,Russell, Angela J.
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p. 3030 - 3054
(2014/05/20)
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- Micelles catalyzed chemoselective synthesis 'in water' and biological evaluation of oxygen containing hetero-1,4-naphthoquinones as potential antifungal agents
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Various oxygen containing 1,4-naphthoquinone derivatives have been synthesized chemoselectively by an economical, viable green methodology approach using water as solvent with or without surfactants such as Triton X-100, SDS, LD (laundry detergent), and T
- Tandon, Vishnu K.,Maurya, Hardesh K.,Mishra, Nripendra N.,Shukla, Praveen K.
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experimental part
p. 6398 - 6403
(2011/12/02)
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- Water-promoted unprecedented chemoselective nucleophilic substitution reactions of 1,4-quinones with oxygen nucleophiles in aqueous micelles
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Unique nucleophilic substitution and addition reactions of nitrogen and sulfur nucleophiles with 1,4-quinones in aqueous suspension with amines and thiols have recently been demonstrated by us.2 However, the reactivity of oxygen nucleophiles toward nucleophilic substitution compared to nitrogen and sulfur nucleophiles 'on water' is not facile. An unprecedented economical, green methodology approach using ordinary laundry detergent (LD; washing powder, 0.5 mol %, reusable)/SDS as surfactant 'in water' for nucleophilic substitution by oxygen nucleophiles in 1,4-quinones in excellent yields has been demonstrated.
- Tandon, Vishnu K.,Maurya, Hardesh K.
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experimental part
p. 3843 - 3847
(2010/08/20)
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- Synthesis of 2-alkoxy 1,4-naphthoquinone derivatives as antiplatelet, antiinflammatory, and antiallergic agents
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In our continuing search for novel antiplatelet, antiallergic, and antiinflammatory agents, 2-alkoxy derivatives of 1,4-naphthoquinone were prepared. Some of these compounds showed significant antiplatelet, antiallergic, and antiinflammatory activities. A
- Lien, Jin-Cherng,Huang, Li-Jiau,Teng, Che-Ming,Wang, Jih-Pyang,Kuo, Sheng-Chu
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p. 672 - 674
(2007/10/03)
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