2-Phenylaminonaphthoquinones and related compounds: Synthesis, trypanocidal and cytotoxic activities

Sieveking, Ivan; Thomas, Pablo; Estévez, Juan C.; Quiñones, Natalia; Cuéllar, Mauricio; Villena, Juan; Espinosa‐Bustos, Christian; Fierro, Angélica; Tapia, Ricardo A.; Maya, Juan Diego; López‐Muñoz, Rodrigo; Cassels, Bruce K.; Estévez, Ramón J.; Salas, Cristian O.

doi:10.1016/j.bmc.2014.07.030

Cited by 62 publications

(75 citation statements)

References 43 publications

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“…In previous studies, our group had reported that the substitution of hydrogen by halogen at C-2 in the quinone moiety increase the selectivity, 13 nevertheless, for halogenated compounds (3d-f, 3h or 3j), there is no a clear pattern. On the other hand, for those of the series II (regarding to 7a, SI = 200), the presence of the β-naphthyl group linked to the naphthoquinone provides an access to more selective compounds (7f).…”

Section: Selectivity Studiesmentioning

confidence: 89%

“…13 For the compounds belonging to the series II (7a-i), the most active were 7f and 7h (IC 50 = 40 and 90 nM respectively). It was found that the incorporation of a withdrawing group in the aryloxy moiety (nitro derivative 3b), enhanced the trypanosomicidal effect and the compound with highest activity (IC 50 = 20 nM) was obtained.…”

Section: Trypanosomicidal Effectmentioning

confidence: 99%

“…Interestingly, 6-phenoxyindolequinone III (Fig. 13 It was found that certain chemical modifications on the naphthoquinone moiety increase the trypanosomicidal and cytotoxic effects. 12 Based on these results, we recently carried out a study of 2-arylaminonaphthoquinone and 5H-benzo[b]carbazole-6,11-dione derivatives.…”

Section: Introductionmentioning

confidence: 99%

“…These compounds were assayed against T. cruzi epi-and trypomastigotes and some of them against cancer cells and normal fibroblasts. 13 On the other hand, quantitative structure-activity relationship (QSAR) studies have emerged as a useful tool to find relevant physicochemical descriptors for the design of new drugs, 16,17 as well as to get some insight into the underlying mechanisms of action of the QSAR-based predicted activities. Several of these compounds were more potent than the reference drug nifurtimox against both stages of the parasite and exhibited increased selectivity against T. cruzi in comparison with VERO cells, being the most active 2-arylaminonaphthoquinone IV (Fig.…”

Section: Introductionmentioning

confidence: 99%

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New aryloxy-quinone derivatives as potential anti-Chagasic agents: synthesis, trypanosomicidal activity, electrochemical properties, pharmacophore elucidation and 3D-QSAR analysis

et al. 2015

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A set of new aryloxy-quinones were synthesized and evaluated in vitro against the epimastigote form of Trypanosoma cruzi and their unspecific cytotoxicity was tested on murine macrophages J-774 cells.Most of these novel compounds were found to be extremely more potent and selective than the standard drug nifurtimox. Interestingly, 2-phenoxy-naphthoquinone 3b displayed a remarkable nanomolar inhibitory activity, IC 50 = 20 nM, and a high selectivity index, SI = 625. The E pc1 was determined for the most interesting compounds and no correlation with the trypanosomicidal effect was found. Therefore, an in silico study was carried out to obtain a pharmacophoric model and quantitative structure-trypanosomicidal activity relationship. The designed pharmacophore recognized the more potent and selective molecules, exhibiting five pharmacophoric features. A correlation coefficient R 2 of 0.99 of pIC 50 plotted against the predicted values indicated that the 3D-QSAR equation could be applied to further predictions of newly designed trypanosomicidal compounds. 5 5a,b with nitric acid. 23 The reaction of 6a and 6b with the phenols 2a-c or naphthols 2d,e furnished regiospecifically the corresponding 7-aryloxy-quinoline-5,8-dione derivatives 7a-i (24-92% yield).Scheme 2. Synthesis of compounds of series II (7a-i). Reagents and conditions: (i) Br 2 , MeOH, rt, 5 min; (ii) HNO 3 , H 2 SO 4 , 0 °C, 30 min; 23 (iii) K 2 CO 3 , 2a-e, DMF, rt, 3-5 h.Scheme 3. Synthesis of compounds of series III (11a-i). Reagents and conditions: (i) Br 2 , CHCl 3 , rt, 1.5 h; (ii) CrO 3 , H 2 O/AcOH, rt, 2 h; (iii) K 2 CO 3 , DMF, 2a-e, rt, 2 h.

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Section: Selectivity Studiesmentioning

confidence: 89%

Section: Trypanosomicidal Effectmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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New aryloxy-quinone derivatives as potential anti-Chagasic agents: synthesis, trypanosomicidal activity, electrochemical properties, pharmacophore elucidation and 3D-QSAR analysis

et al. 2015

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“…They have three oxidation states; one state is quinone, another state is semiquinone, which is oneelectron reduced form of quinone, and the last one is also catechol or hydroquinone which is two-electron reduced form of quinone. These different oxidation states of quinone structures make them very crucial for chemical science (1). For instance, the reduction properties of quinones stand out in the field of energy storage.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Structural Analysis of Some New Sulfanyl Amino 1,4-Naphthoquinone Derivatives

Yıldırım

2017

Journal of the Turkish Chemical Society, Section A: Chemistry

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In this study, some new sulfanyl-substituted amino 1,4-naphthoquinone derivatives which possess two electron-donating groups in the amino fragment were synthesized and their structures were analyzed by spectroscopic techniques. First, 2-chloro-3-[(2,4dimethoxyphenyl)amino]naphthalene-1,4-dione (3a) and 2-chloro-3-[(3,5dimethoxyphenyl)amino]naphthalene-1,4-dione (3b) were obtained from the reactions of dichloro-1,4-naphthoquinone (1) with 2,4-dimethoxyaniline and 3,5-dimethoxyaniline. In the following step, the compounds 3a,b were reacted with aliphatic nucleophiles; ethyl-, 1-propyl-, and 1-pentyl mercaptan. S-nucleophiles attacked the carbon atom of 1,4-naphthoquinone core and displaced the chlorine atom to create target molecules; 2-arylamino-3-(ethylthio)naphthalene-1,4-dione (5a,b), 2-arylamino-3-(propylthio)naphthalene-1,4-dione (5c,d), 2-arylamino-3-(pentylthio)naphthalene-1,4-dione (5e,f) derivatives. The structures of the synthesized compounds were elucidated by utilizing 1D and 2D NMR techniques with additional spectroscopic data (mass and FTIR).

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Palladium‐Catalyzed Regioselective Synthesis of 1‐Hydroxycarbazoles Under Aerobic Conditions

Youn

Kim

2018

Adv Synth Catal

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A palladium-catalyzed aerobic CÀH amidation of N-Ts-2-amino-3'-hydroxylbiaryls has been developed to afford a diverse range of 1-hydroxycarbazoles with high regioselectivity and efficiency. This protocol benefits from operational simplicity, robustness, and sustainability with the use of ambient air as the sole terminal oxidant. Further elaboration of the products obtained from this process provides facile access to various carbazole alkaloids including carbazolequinones and biscarbazoles. A mechanism involving dual directing group-assisted regioselective CÀH activation at the more sterically hindered C2'-position of 2-amino-3'-hydroxylbiaryls is proposed.

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2-Phenylaminonaphthoquinones and related compounds: Synthesis, trypanocidal and cytotoxic activities

Cited by 62 publications

References 43 publications

New aryloxy-quinone derivatives as potential anti-Chagasic agents: synthesis, trypanosomicidal activity, electrochemical properties, pharmacophore elucidation and 3D-QSAR analysis

New aryloxy-quinone derivatives as potential anti-Chagasic agents: synthesis, trypanosomicidal activity, electrochemical properties, pharmacophore elucidation and 3D-QSAR analysis

Synthesis and Structural Analysis of Some New Sulfanyl Amino 1,4-Naphthoquinone Derivatives

Palladium‐Catalyzed Regioselective Synthesis of 1‐Hydroxycarbazoles Under Aerobic Conditions

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