Synthesis and cytotoxic activities of 6-chloro-7-arylamino-5,8-isoquinolinediones

Ryu, Chong Kul; Lee, Inkyung; Jung, Sung-Hee; Lee, Chong‐Ock

doi:10.1016/s0960-894x(99)00152-3

Cited by 18 publications

(8 citation statements)

References 11 publications

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“…Both JUN 379 and JUN 390 were prepared by methods described previously (Draber, 1967;Nohara et al, 1974). JUN 255 and the corresponding isoquinone analog, JUN 260, were synthesized by treating a solution of 2-(tetrahydropyran-2-yloxy)ethanethiol (Li et al, 1999) and either 6,7-dichloroquinoline-5,8-dione or the corresponding isoquinoline (Ryu et al, 1999) in tetrahydrofuran at room temperature with triethylamine. The reaction mixture was stirred for 20 h, concentrated under reduced pressure, diluted with ethyl acetate, and washed with water.…”

Section: Methodsmentioning

confidence: 99%

Identification of a Potent and Selective Pharmacophore for Cdc25 Dual Specificity Phosphatase Inhibitors.

et al. 2002

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Small molecules provide powerful tools to interrogate biological pathways but many important pathway participants remain refractory to inhibitors. For example, Cdc25 dual-specificity phosphatases regulate mammalian cell cycle progression and are implicated in oncogenesis, but potent and selective inhibitors are lacking for this enzyme class. Thus, we evaluated 10,070 compounds in a publicly available chemical repository of the National Cancer Institute for in vitro inhibitory activity against oncogenic, full-length, recombinant human Cdc25B. Twenty-one compounds had mean inhibitory concentrations of Ͻ1 M; Ͼ75% were quinones and Ͼ40% were of the paranaphthoquinone structural type. Most notable was NSC 95397 (2,3-bis-[2-hydroxyethylsulfanyl]-[1,4]naphthoquinone), which displayed mixed inhibition kinetics with in vitro K i values for Cdc25A, -B, and -C of 32, 96, and 40 nM, respectively. NSC 95397 was more potent than any inhibitor of dual specificity phosphatases described previously and 125-to 180-fold more selective for Cdc25A than VH1-related dual-specificity phosphatase or protein tyrosine phosphatase 1b, respectively. Modification of the bis-thioethanol moiety markedly decreased enzyme inhibitory activity, indicating its importance for bioactivity. NSC 95397 showed significant growth inhibition against human and murine carcinoma cells and blocked G 2 /M phase transition. A potential Cdc25 site of interaction was postulated based on molecular modeling with these quinones. We propose that inhibitors based on this chemical structure could serve as useful tools to probe the biological function of Cdc25.

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Section: Methodsmentioning

confidence: 99%

Identification of a Potent and Selective Pharmacophore for Cdc25 Dual Specificity Phosphatase Inhibitors.

et al. 2002

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“…A small library of arylamine derivatives of 5,8-quinolinedione were prepared by Ryu et al [50,55,56].…”

Section: Biological Activitymentioning

confidence: 99%

“…Natural 5,8-quinolinedione antibiotics contain an amine group at the C-7 position; for this reason, Ryu et al obtained 7-arylamine-6-chloro-5,8-quinolinedione 21 – 23 (Figure 3) [56]. The study showed that compounds 16 – 18 and 21 – 23 had a similar activity against the SK-OV-3 and SK-MEL-2 cell lines.…”

Section: Biological Activitymentioning

confidence: 99%

“…The study showed that compounds 16 – 18 and 21 – 23 had a similar activity against the SK-OV-3 and SK-MEL-2 cell lines. The 7-arylamine-6-chloro-5,8-quinolinedines 21 – 23 was characterized by a lower activity against lung cancer (A549) than derivatives 16 – 18 (Figure 3) [55,56]. In the series of 7-arylamine compounds 21 – 23 , the lowest IC 50 value against the A549 cell line was exhibited by 6-chloro-7-(4-fluorphenylamine)-5,8-quinolinedione 22 , having activity comparable with that of cisplatin (IC 50 = 1.80 µg/mL) [56].…”

Section: Biological Activitymentioning

confidence: 99%

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5,8-Quinolinedione Scaffold as a Promising Moiety of Bioactive Agents

et al. 2019

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Natural 5,8-quinolinedione antibiotics exhibit a broad spectrum of activities including anticancer, antibacterial, antifungal, and antimalarial activities. The structure–activity research showed that the 5,8-quinolinedione scaffold is responsible for its biological effect. The subject of this review report is a presentation of the pharmacological activity of synthetic 5,8-quinolinedione compounds containing different groups at C-6 and/or C-7 positions. The relationship between the activity and the mechanism of action is included if these data have been included in the original literature. The review mostly covers the period between 2000 and 2019. Previously published literature data were used to present historical points.

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“…), and many synthetic or natural quinones possess various pharmacological properties including anticancer [3][4][5], antibacterial [6], antifungal [6], antiinflammatory [7], antimycobacterial [8], and molluscicidal [9] activities. Moreover, substituents such as halogen, amino, thio groups of the synthetic quinone derivatives can increase their pharmacological activities, such as antibacterial, cytotoxic, and antiproliferative [3,10,11]. Quinonoid systems' pharmacological specialties are related to their capacity to produce free radicals or semiquinones in redox reactions [11][12][13].Among quinones, 1,4-naphthoquinone scaffold are found in many natural or synthetic products such as menadione, juglone, plumbagin, alkannin, and shikonin [14-16].…”

mentioning

confidence: 99%

Synthesis of some NH- and NH,S- substituted 1,4-quinones

Kaçmaz

2021

Turk J Chem

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IntroductionQuinones are widespread in nature [1,2] (in plants, fungi, bacteria etc.), and many synthetic or natural quinones possess various pharmacological properties including anticancer [3][4][5], antibacterial [6], antifungal [6], antiinflammatory [7], antimycobacterial [8], and molluscicidal [9] activities. Moreover, substituents such as halogen, amino, thio groups of the synthetic quinone derivatives can increase their pharmacological activities, such as antibacterial, cytotoxic, and antiproliferative [3,10,11]. Quinonoid systems' pharmacological specialties are related to their capacity to produce free radicals or semiquinones in redox reactions [11][12][13].Among quinones, 1,4-naphthoquinone scaffold are found in many natural or synthetic products such as menadione, juglone, plumbagin, alkannin, and shikonin [14-16]. In addition, 1,4-naphthoquinone derivatives have receieved a considerable interest in biological applications with their antibacterial [11], antiatherosclerosis [17], antiinflammatory [18], anticancer [5,18], and cytotoxic [19] activities. Thus, many reports on the reactions of 1,4-naphthoquinones with amines [3,5,13], anilines [11,20], phenols [21], thiols [3,5,22], aminopyridine [23], alcohol [24,25], glycol [25] are available in the literature. In this study, compounds 10, 12, 13, 15, 17, and 19, 20 have NH-and NH,SR-substituted-1,4-naphthoquinone skeleton, respectively.The literature mentions some aminobenzocrown ethers [26,27] similar to 15 and 17. For example, N-(2-chloro-1,4naphthoquinon-3-yl)-4'-aminobenzocrown ethers were synthesized from the reaction between 4'-aminobenzocrown ethers and 2,3-dichloro-1,4-naphthoquinone [26], and thus in the present study, synthesis of 15 and 17 contribute to crown-containing naphthoquinones, carrying out the reaction between crown ethers (14 and 16) and 2-bromo-1,4naphthoquinone (4). Moreover, crown-containing naphthoquinone 19 was synthesized, including both amino and thio substituents, together.1,4-benzoquinones, including NH-, methoxy, thio, alkyl or aryl groups, have been the subject of study due to their properties such as antimicrobial [28], antibacterial [29], cytotoxic [30][31][32], potential urease inhibitor [33], and potent inhibitory activity towards enzyme system [34]. In addition, some of studies on the formation of N(H)-, SR-, alkoxy substituted-1,4-benzoquinones have been reported in the literature [34][35][36][37][38]. Among 1,4-benzoquinones, halogenanils, such as chloranil, with amines yield amination products of quinones. For example, Wu H et al. reported tetrathiafulvalenequinone dyad, having mono-NH-substituted-tri-chloro-1,4-benzoquinone structure [38]. In another example, Sing and et al. synthesized [39] new coordination polymers, starting from 2,5-dichloro-3,6-bis(ethylamino)-1,4-benzoquinone. In this study, compounds 6 and 7 have mono-NH-substituted-tri-chloro-1,4-benzoquinone and 2,5-dichloro-3,6-bis(NH-

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Synthesis and cytotoxic activities of 6-chloro-7-arylamino-5,8-isoquinolinediones

Cited by 18 publications

References 11 publications

Identification of a Potent and Selective Pharmacophore for Cdc25 Dual Specificity Phosphatase Inhibitors.

Identification of a Potent and Selective Pharmacophore for Cdc25 Dual Specificity Phosphatase Inhibitors.

5,8-Quinolinedione Scaffold as a Promising Moiety of Bioactive Agents

Synthesis of some NH- and NH,S- substituted 1,4-quinones

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