Synthesis and Biological Evaluation of Benzo[f]indole-4,9-diones N-Linked to Carbohydrate Chains as New Type of Antitumor Agents

Dias, Flaviana R. F.; Guerra, Fabiana Sélos; Lima, Fernanda A.; Castro, Yasmin K. C. de; Ferreira, Vı́tor F.; Campos, Vinícius R.; Fernandes, Patrícia Dias; Cunha, Anna C.

doi:10.21577/0103-5053.20200202

Cited by 4 publications

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“…Our current data demonstrate that all compounds significantly inhibited proliferation and induced apoptosis in MDA-MB 231 cells. Consistent with our prior study [ 14 ], we showed that benzo[ f ]indole-4,9-dione derivatives are promising therapeutic agents for the induction of apoptosis, specifically in highly proliferative and metabolically active TNBC cells, without seriously affecting normal cells. We could see that the four structurally related indoles showed similar biological patterns.…”

Section: Discussionsupporting

confidence: 92%

“…The compounds LACBio1, LACBio2, LACBio3 and LACBio4 investigated in this work were synthesized as previously described by Dias and colleagues [ 14 ]. The synthesis of the compounds LACBio1 and LACBio2 involved the reaction of halo-naphthoquinones containing a carbonyl group with amino carbohydrates.…”

Section: Methodsmentioning

confidence: 99%

“…We have previously synthesized three series of carbohydrate-based benzo[ f ]índole-4,9-diones and amino-1,4-naphthoquinone derivatives and evaluated their cytotoxic activity by MTT assay against eight human cancer cell lines and nontumor human erythrocytes [ 14 ]. From this study, we choose four benzo[ f ]indole-4,9-dione derivatives, LACBio1, LACBio2, LACBio3 and LACBio4, and evaluated their action against the TNBC cells MDA-MB 231.…”

Section: Introductionmentioning

confidence: 99%

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Benzo[f]indole-4,9-dione Derivatives Effectively Inhibit the Growth of Triple-Negative Breast Cancer

et al. 2021

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Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor clinical outcome, and currently no effective targeted therapies are available. Indole compounds have been shown to have potential antitumor activity against various cancer cells. In the present study, we found that new four benzo[f]indole-4,9-dione derivatives reduce TNBC cell viability by reactive oxygen species (ROS) accumulation stress in vitro. Further analyses showed that LACBio1, LACBio2, LACBio3 and LACBio4 exert cytotoxic effects on MDA-MB 231 cancer cell line by inducing the intrinsic apoptosis pathway, activating caspase 9 and Bax/Bcl-2 pathway in vitro. These results provide evidence that these new four benzo[f]indole-4,9-dione derivatives could be potential therapeutic agents against TNBC by promoting ROS stress-mediated apoptosis through intrinsic-pathway caspase activation.

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Section: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Benzo[f]indole-4,9-dione Derivatives Effectively Inhibit the Growth of Triple-Negative Breast Cancer

et al. 2021

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“…The 1-arylhydrazono-1chloroacetones (1a-f) were then coupled with 1-naphthylamine to yield the corresponding arylamidrazones (2a-f), which are then cyclized using polyphosphoric acid (PPA) as a catalyst to produce benzo[g]indole target products (3a-f) in a 50-60% yield. bromodomain and extra-terminal (BET) inhibition, anticancer effects, non-covalent Keap1-Nrf2 protein-protein interaction inhibition, and microsomal prostaglandin E2 synthase-1 inhibition [11][12][13][14][15][16][17][18][19][20]. The incorporation of azo moiety as a structural motif has enhanced the cytotoxicity of various systems [21,22].…”

Section: Synthesis Of Benzo[g]indolesmentioning

confidence: 99%

“…During the last decade, various benzo[g]indoles have been synthesized and found to exhibit a broad spectrum of biological activities, among which the interchelating anti-tumor activity is of considerable pharmaceutical interest [10]. Certain benzoindoles are useful structures with interesting bioactivities, such as LOX inhibition, bromodomain and extra-terminal (BET) inhibition, anticancer effects, non-covalent Keap1-Nrf2 protein-protein Molecules 2021, 26, 4240 2 of 14 interaction inhibition, and microsomal prostaglandin E2 synthase-1 inhibition [11][12][13][14][15][16][17][18][19][20]. The incorporation of azo moiety as a structural motif has enhanced the cytotoxicity of various systems [21,22].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Cytotoxic Activity Study of Novel 2-(Aryldiazenyl)-3-methyl-1H-benzo[g]indole Derivatives

et al. 2021

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A novel series of 2-(aryldiazenyl)-3-methyl-1H-benzo[g]indole derivatives (3a–f) were prepared through the cyclization of the corresponding arylamidrazones, employing polyphosphoric acid (PPA) as a cyclizing agent. All of the compounds (3a–f) were characterized using 1H NMR, 13C NMR, MS, elemental analysis, and melting point techniques. The synthesized compounds were evaluated for cytotoxic activity against diverse human cancer cell lines by the National Cancer Institute. While all of the screened compounds were found to be cytotoxic at a 10 µM concentration, two of them (2c) and (3c) were subjected to five dose screens and showed a significant cytotoxicity and selectivity.

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Theoretical Investigation of Regiodivergent Addition of Anilines and Phenolates to p-Benzoquinone Ring

et al. 2022

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Two different products were obtained by the regiodivergent reaction of benzoquinone derivatives with phenolates and anilines: 3-aryloxybenzoquinone and 2-phenylamino-3-bromobenzoquinone. Calculated density functional theory free energies of reaction values corroborate the experimental observation of the formation of the substitution product in the reaction with phenolates in acetonitrile and the product of addition/oxidation for the reaction with aniline in water. Calculated charges and Fukui functions are similar for C2 and C3 atoms, indicating an equal possibility to suffer a nucleophilic attack. The calculated energy barriers for nucleophilic attack steps indicated that the first steps of the substitution with phenolates and addition/oxidation with anilines are faster, which justifies the formation of the respective products. The natural bond order analysis for the transition states revealed that there is a strong interaction between lone pairs of N and O atoms and the πC2C3 * for the O → C2 and N → C3 attacks and a weak interaction for the O → C3 and N → C2 attacks, which also agrees with experimental observations.

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Synthesis and Biological Evaluation of Benzo[f]indole-4,9-diones N-Linked to Carbohydrate Chains as New Type of Antitumor Agents

Cited by 4 publications

References 0 publications

Benzo[f]indole-4,9-dione Derivatives Effectively Inhibit the Growth of Triple-Negative Breast Cancer

Benzo[f]indole-4,9-dione Derivatives Effectively Inhibit the Growth of Triple-Negative Breast Cancer

Synthesis and Cytotoxic Activity Study of Novel 2-(Aryldiazenyl)-3-methyl-1H-benzo[g]indole Derivatives

Theoretical Investigation of Regiodivergent Addition of Anilines and Phenolates to p-Benzoquinone Ring

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