New 3-tetrazolyl-β-carbolines and β-carboline-3-carboxylates with anti-cancer activity

Panice, Manuela Ribeiro; Lopes, Susana M. M.; Figueiredo, Mariana Cecchetto; Ruiz, Ana Lúcia T. G.; Foglio, Mary Ann; Formagio, Anelise Samara Nazari; Sarragiotto, María Helena; Melo, Teresa M. V. D. Pinho e

doi:10.1016/j.ejmech.2019.05.085

Cited by 21 publications

(15 citation statements)

References 47 publications

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“…In fact, the open-chain oximes were isolated as single isomers, with the hydroxyl and pyrrolylmethyl or indolylmethyl groups cis as expected for a mechanism pathway involving a hetero-Diels–Alder reaction and subsequent ring-opening reaction of the bicyclic 1,2-oxazine. In addition, pyrrole was functionalized at position 2 whereas the reaction with indole gave a 3-alkylated derivative which is in agreement with the expected and opposite regioselectivity of the hetero-Diels–Alder reaction. − …”

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confidence: 78%

One-Pot Synthetic Approach to Dipyrromethanes and Bis(indolyl)methanes via Nitrosoalkene Chemistry

et al. 2021

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A one-pot regio-and stereoselective synthesis of a dipyrromethane and a bis(indolyl)methane based on two consecutive reactions of nitrosoalkenes with pyrrole or indole, respectively, is described as an experiment to be carried out by upper-division undergraduate students in a laboratory classroom. Importantly, the ability of electrophilic conjugated nitrosoalkenes to react via Michael addition or hetero-Diels− Alder reactions with electron-rich heterocycles will provide an opportunity for students to acknowledge alternative reaction pathways underlying certain transformations. Reactions were performed under mild conditions using water as a solvent, followed by purification through column chromatography on silica gel, and characterization of the desired products by NMR and IR spectroscopy. This laboratory experiment combines organic synthesis, determination of the purity of compounds (TLC analysis and melting point measurements), as well as structural analysis (interpretation of 1D NMR spectra). Several important organic chemistry concepts, such as stereo-and regioselectivity, in situ generation and reactivity of conjugated nitrosoalkenes, conjugated 1,4-addition reactions, and cycloaddition reactions, are also discussed.

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confidence: 78%

One-Pot Synthetic Approach to Dipyrromethanes and Bis(indolyl)methanes via Nitrosoalkene Chemistry

et al. 2021

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“…b-carbolines are biologically active alkaloids, and these compounds have been reported to possess a wide range of biological effects, such as anti-inflammatory, antithrombotic activities, antivirus, anticancer and free radical scavenging activities [46]. Previous studies demonstrated the potential application of b-carboline derivatives in the treatment of cardiovascular diseases like hypertension [47], myocardial infarction [25], [48], cancer [49][50][51][52], and ischemia/reperfusion injury [53][54][55][56][57][58][59]. In addition, 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl (Tempol) has gained attention.…”

Section: Discussionmentioning

confidence: 99%

A Novel Mitophagy Enhancer Protects Cardiomyocytes against Hypoxia/Reoxygenation

Yan¹,

Gao²,

Hou³

et al. 2022

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Ischemia/reperfusion (I/R) injury results in cell death by inducing apoptosis. During I/R, early generation of mitochondrial reactive oxygen species (mtROS) can induce neighboring mitochondria to release additional ROS, a toxic cycle resulting in significant mitochondrial and cellular injury. Oxidative damage in the mitochondria contributes to various pathologies, including I/R injury. Accordingly, preventing mitochondrial oxidative damage should be therapeutically relevant for many disorders, including cardiovascular diseases. We recently discovered an Indole-Peptide-Tempo Conjugate (IPTC) that served as a novel bifunctional agent with both antioxidant and autophagy-modulating capacity. Here, we demonstrate that IPTC can protect H9C2 cardiomyocytes from hypoxia/reoxygenation (H/R) injury that results from mtROS overproduction due to impaired mitophagy and resultant mitochondrial dysfunction. We hypothesize that the mechanism of action of IPTC involves the capacity to decrease mtROS combined with induction of mitophagy.

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“…β-Carbolines are a class of indole-based natural and synthetic compounds bearing a 9H-pyrido [3,4-b]indole scaffold, with a wide range of biological activities, such as anti-HIV [2][3][4], antibacterial [3][4][5], antimalarial [6,7], and anticancer [8,9], among others [10][11][12]. It is noteworthy to mention their anticancer activity, which has been extensively studied in recent years by several groups, with promising results [5,8,9,[13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

3-(1,2,3-Triazol-4-yl)-β-Carbolines and 3-(1H-Tetrazol-5-yl)-β-Carbolines: Synthesis and Evaluation as Anticancer Agents

et al. 2022

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Herein, the synthesis and anticancer activity evaluation of a series of novel β-carbolines is reported. The reactivity of nitrosoalkenes towards indole was explored for the synthesis of novel tryptophan analogs where the carboxylic acid was replaced by a triazole moiety. This tryptamine was used in the synthesis of 3-(1,2,3-triazol-4-yl)-β-carbolines via Pictet–Spengler condensation followed by an oxidative step. A library of compounds, including the novel 3-(1,2,3-triazol-4-yl)-β-carbolines as well as methyl β-carboline-3-carboxylate and 3-tetrazolyl-β-carboline derivatives, was evaluated for their antiproliferative activity against colorectal cancer cell lines. The 3-(1H-tetrazol-5-yl)-β-carbolines stood out as the most active compounds, with values of half-maximal inhibitory concentration (IC50) ranging from 3.3 µM to 9.6 µM against colorectal adenocarcinoma HCT116 and HT29 cell lines. The results also revealed a mechanism of action independent of the p53 pathway. Further studies with the 3-tetrazolyl-β-carboline derivative, which showed high selectivity for cancer cells, revealed IC50 values below 8 μM against pancreatic adenocarcinoma PANC-1, melanoma A375, hepatocarcinoma HEPG2, and breast adenocarcinoma MCF-7 cell lines. Collectively, this work discloses the 3-tetrazolyl-β-carboline derivative as a promising anticancer agent worthy of being further explored in future works.

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New 3-tetrazolyl-β-carbolines and β-carboline-3-carboxylates with anti-cancer activity

Cited by 21 publications

References 47 publications

One-Pot Synthetic Approach to Dipyrromethanes and Bis(indolyl)methanes via Nitrosoalkene Chemistry

One-Pot Synthetic Approach to Dipyrromethanes and Bis(indolyl)methanes via Nitrosoalkene Chemistry

A Novel Mitophagy Enhancer Protects Cardiomyocytes against Hypoxia/Reoxygenation

3-(1,2,3-Triazol-4-yl)-β-Carbolines and 3-(1H-Tetrazol-5-yl)-β-Carbolines: Synthesis and Evaluation as Anticancer Agents

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