17173-25-0Relevant academic research and scientific papers
Identification of β-lapachone analogs as novel MALT1 inhibitors to treat an aggressive subtype of diffuse large B-cell lymphoma
Lim, Sang Min,Jeong, Yujeong,Lee, Suhyun,Im, Honggu,Tae, Hyun Seop,Kim, Byung Gyu,Park, Hee Dong,Park, Jonghoon,Hong, Sungwoo
, p. 8491 - 8502 (2015)
The treatment of activated B cell-like DLBCL (ABC-DLBCL) is one of the urgent unmet medical needs because it is the most resistant DLBCL subtype to current therapies eagerly awaiting effective therapeutic strategies. Recently, the paracaspase MALT1 has emerged as a promising therapeutic target for the treatment of ABC-DLBCL. Herein, we report a new class of MALT1 inhibitors developed by high-throughput screening and structure-based drug design. The original hit, 4-amino-1,2-naphthoquinone series inhibited MALT1 activity but suffered from poor cellular activity. The extensive pharmacophore search led to the discovery of structurally similar β-lapachone that is a direct inhibitor of MALT1 and possesses favorable physicochemical properties. Molecular simulation studies suggested the possibility of the formation of a covalent bond between MALT1 and β-lapachone, which was corroborated by experimental wash-out studies. Inspired by this, we explored the structure-activity relationships by incorporating electron-withdrawing substituents at C8 position of β-lapachone. These MALT1 inhibitors exhibited potent antiproliferative activity to OCI-LY3 cell line and inhibited the cleavage of CYLD mediated MALT1.
Synthesis and biological evaluation of β-lapachone-monastrol hybrids as potential anticancer agents
Wu, Liqiang,Ma, Xin,Yang, Xiaojuan,Zhang, Chong
, (2020)
A series of novel β-lapachone analogs was designed and synthesized by replacing pyran ring of β-lapachone with tetrahydropyrimidinethione moiety of monastrol. These hybrids had potent antiproliferative activity against NQO1-rich cell lines (HepG2 and A549
Design, synthesis, and biological evaluation of 3-(1-benzotriazole)-nor-β-lapachones as NQO1-directed antitumor agents
Wu, Li-Qiang,Ma, Xin,Liu, Zhao-Peng
, (2021/05/27)
A series of novel 3-(1-benzotriazole)-nor-β-lapachones 5a–5l were synthesized as the NQO1-targeted anticancer agents. Most of these compounds displayed good antiproliferative activity against the breast cancer MCF-7, lung cancer A549 and hepatocellular ca
NAPTHOQUINONES, PRO-DRUGS, AND METHODS OF USE THEREOF
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Paragraph 00119; 00131; 00146, (2017/07/06)
Provided herein are naphthoquinones compounds such as those with a hydrogen bond donating group of the formula (I): wherein: R1, R2, R3, R4, R5, and n are as defined herein. Also provided herein are pharmaceutical composition of the present compounds and methods of treatment using the compounds including their use in the treatment of cancer.
Antiviral agents 2. Synthesis of trimeric naphthoquinone analogues of conocurvone and their antiviral evaluation against HIV
Crosby, Ian T.,Bourke, David G.,Jones, Eric D.,De Bruyn, Paula J.,Rhodes, David,Vandegraaff, Nick,Cox, Susan,Coates, Jonathan A.V.,Robertson, Alan D.
experimental part, p. 6442 - 6450 (2010/10/04)
The synthesis of a new series of conocurvone analogues is presented that explores the importance of the pyran rings of conocurvone, their degree of unsaturation as well as the role of alkoxy functionalities as pyran ring replacements, for the inhibition of the HIV-1 integrase (IN) enzyme. Difficulties in synthesising a trimeric naphthoquinone where the central quinone bears a peri-dihydropyran ring was attributed to distortion of the electrophilic dihaloquinone successfully utilised in the past. Increased electron density could also be a factor in reducing reactivity. The desired central dihydropyran bearing trimeric naphthoquinone was successfully synthesised by using a more reactive bromo-tosyloxyquinone intermediate. A maleimide derivative, where the central quinone between the pendant hydroxyquinones was replaced, was successfully synthesised and although it exhibited comparable enzyme inhibitory activity it had negligible HIV inhibitory cellular activity. Compounds were assessed for activity in both in vitro assays using purified recombinant HIV-1 IN and demonstrated superior or comparable activity to conocurvone derivatives previously reported.
Synthesis and antiallergic activity of 2 hydroxy 3 nitro 1,4 naphthoquinones
Buckle,Cantello,Smith,Spicer
, p. 1059 - 1064 (2007/10/06)
A selection of novel 2-hydroxy-3-nitro-1,4-naphthoquinones are shown to be potent inhibitors of rat passive cutaneous anaphylaxis (PCA) and to have highest potency with alkyl substitution at both C-6 and C-7. The most potent compounds were 7c and 7e which produced a 50% inhibition in the rat PCA test at doses of about 10 μM/kg following subcutaneous administration and showed activity after oral administration. Related 4-hydroxy-3-nitro-2(1H)-naphthalenones had no effect on rat PCA in doses up to 500 μM/kg.
