Inspired by bis-β-carboline alkaloids: Construction and antitumor evaluation of a novel bis-β-carboline scaffold as potent antitumor agents

Liu, Wei; Wang, Miaomiao; Guo, Zhongjie; He, Youyou; Jia, Hairui; He, Jin; Miao, Shanshan; Ding, Yi; Wang, Shengzheng

doi:10.1016/j.bioorg.2023.106401

Cited by 3 publications

(8 citation statements)

References 40 publications

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“…I n vitro antitumor activity was conducted using the CCK-8 method. − The solid tumor cell lines HepG2 (liver cancer cell), A549 (lung cancer cell), HCT116 (colon cancer cell), MDA-MB-231 (triple-negative breast cancer cell), and CDDP-resistant A549 (A549/CDDP) were used in this study. CDDP, ATS, and the mixture (ATS plus CDDP, 1:1) were used as the positive control.…”

Section: Resultsmentioning

confidence: 99%

Discovery of Platinum^IV–Artesunate Multiaction Prodrugs as Potent Antitumor and Antimalarial Agents

Liu

Wang

et al. 2023

J. Med. Chem.

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Recently, artemisinin and derivatives have been revealed to possess encouraging antitumor activity. Herein, we integrated the antitumor advantages of artesunate and platinum drugs to construct novel Pt IV −artesunate dual-action and tripleaction complexes. Most derivatives, especially 10f, displayed broadspectrum and potent in vitro antitumor activities against a number of cancer cell lines. Compound 10f displayed potent antimetastasis and anticlonogenic activities, efficiently induced autophagic cell death and apoptosis, and arrested the cell cycle at both S and G2/M phases. More importantly, it displayed remarkable in vivo antitumor efficacy in the A549 xenograft model (TGI = 53.4%; 6 μmol/kg) with low toxicity. In addition to the antitumor application, 10f showed potent in vivo antimalarial activity in malarial-infected mice model and obviously alleviated malarial-related multiorgan injury. This conjugation greatly improved safety, especially reducing the platinum drugs' nephrotoxicity. Taken together, this study highlighted the therapeutic potential of Pt IV −artesunate complexes as antitumor and antimalarial agents.

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Section: Resultsmentioning

confidence: 99%

Discovery of Platinum^IV–Artesunate Multiaction Prodrugs as Potent Antitumor and Antimalarial Agents

Liu

Wang

et al. 2023

J. Med. Chem.

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“…Mitochondria-mediated caspase activation pathway triggered by DNA damage, overexpression of intracellular reactive oxygen species (ROS), etc., is a major apoptotic pathway, which is classically characterized by mitochondrial outer membrane permeabilization [ 22 ]. JC-1 (5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanine) dye is widely used to detect mitochondrial membrane potential (MMP, ΔΨm), which present red fluorescence (aggregates) for normal MMP [ 23 ].…”

Section: Resultsmentioning

confidence: 99%

“…The overexpression of intracellular ROS can induce oxidative stress damage such as lipids and DNA, and further result to cell apoptosis. Previous study indicated that β -carboline alkaloids could increase the intracellular ROS level in A549 cells and thus triggered the cell apoptosis [ 22 ]. Mitochondria is the main site of reactive oxygen species production.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of 3-formyl-eudistomin U with anti-proliferation, anti-migration and apoptosis-promoting activities on melanoma cells

Gao,

Liu,

et al. 2023

BMC Chemistry

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The discovery of new lead skeleton against melanoma are urgently needed due to its highly malignant and mortality. Herein, a new molecular entity (EU-5) derived from eudistomin U was synthesized with total yield of 46%, which displayed potent activity against malignant melanoma A375 cells (IC50 = 4.4 µM), no hemolytic toxicity and good physicochemical properties in silico. Colony formation and cell cycle arrest assays revealed that EU-5 suppressed cell proliferation by causing cell cycle arrest at G0/G1 phase. Wound healing and transwell assays suggested that EU-5 could effectively inhibit migration of A375 cells in a dose-dependent manner. Calcein-AM/PI staining, Annexin V-FITC/PI apoptosis detection, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), transcriptomics, quantitative real‑time polymerase chain reaction (qRT‑PCR), spectrometric titration and molecular docking assays indicated that EU-5 could activate p53 signaling pathway and trigger mitochondria-mediated cell apoptosis. Taken together, this study provided a promising lead structure for the design of a new generation of anti-melanoma drugs.

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“…β-Carboline alkaloids are widely distributed in nature. 14 Because of their broad spectrum of biological activities, 15−22 βcarboline alkaloids have been extensively investigated in pharmaceutical science. In our previous work, 1-carbamoyl βcarbolines were found to display promising in vitro antifungal activities against Ggt, of which 4m and 4i exhibited up to >10fold improvements in inhibitory activity against Ggt compared to that of silthiopham.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Owing to their fewer adverse environmental effects, bioactive natural products can be used as ideal leads to develop rational alternatives to commonly used pesticides. β - Carboline alkaloids are widely distributed in nature . Because of their broad spectrum of biological activities, − β - carboline alkaloids have been extensively investigated in pharmaceutical science.…”

Section: Introductionmentioning

confidence: 99%

Chromatography-Free Synthesis of β-Carboline 1-Hydrazides and an Investigation of the Mechanism of Their Bioactivity: The Discovery of β-Carbolines as Promising Antifungal and Antibacterial Candidates

Sheng

Wang

et al. 2023

J. Med. Chem.

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Agrochemical science prioritizes the discovery and effective synthesis of innovative and promising lead compounds. Herein, we developed an efficient column chromatography-free synthesis for β-carboline 1-hydrazides via a mild CuBr2-catalyzed oxidation and investigated the antifungal and antibacterial activities and mechanisms for these compounds. In our study, compounds 4de (EC50 = 0.23 μg·mL–1) and 4dq (EC50 = 0.11 μg·mL–1) displayed the best efficacy, demonstrating enhancements in inhibitory activity of more than 20-fold against Ggt compared to silthiopham (EC50 = 2.39 μg·mL–1). Additionally, compound 4de (EC50 = 0.21 μg·mL–1) demonstrated outstanding in vitro antifungal activities as well as in vivo curative activities against Fg. According to preliminary mechanistic studies, β-carboline 1-hydrazides led to the accumulation of reactive oxygen species, destruction of cell membranes, and dysregulation of histone acetylation. Furthermore, several substances exhibited antibacterial activity against Psg and Cms by preventing the development of bacterial biofilms.

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Inspired by bis-β-carboline alkaloids: Construction and antitumor evaluation of a novel bis-β-carboline scaffold as potent antitumor agents

Cited by 3 publications

References 40 publications

Discovery of Platinum^IV–Artesunate Multiaction Prodrugs as Potent Antitumor and Antimalarial Agents

Discovery of Platinum^IV–Artesunate Multiaction Prodrugs as Potent Antitumor and Antimalarial Agents

Synthesis of 3-formyl-eudistomin U with anti-proliferation, anti-migration and apoptosis-promoting activities on melanoma cells

Chromatography-Free Synthesis of β-Carboline 1-Hydrazides and an Investigation of the Mechanism of Their Bioactivity: The Discovery of β-Carbolines as Promising Antifungal and Antibacterial Candidates

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Inspired by bis-β-carboline alkaloids: Construction and antitumor evaluation of a novel bis-β-carboline scaffold as potent antitumor agents

Cited by 3 publications

References 40 publications

Discovery of PlatinumIV–Artesunate Multiaction Prodrugs as Potent Antitumor and Antimalarial Agents

Discovery of PlatinumIV–Artesunate Multiaction Prodrugs as Potent Antitumor and Antimalarial Agents

Synthesis of 3-formyl-eudistomin U with anti-proliferation, anti-migration and apoptosis-promoting activities on melanoma cells

Chromatography-Free Synthesis of β-Carboline 1-Hydrazides and an Investigation of the Mechanism of Their Bioactivity: The Discovery of β-Carbolines as Promising Antifungal and Antibacterial Candidates

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Discovery of Platinum^IV–Artesunate Multiaction Prodrugs as Potent Antitumor and Antimalarial Agents

Discovery of Platinum^IV–Artesunate Multiaction Prodrugs as Potent Antitumor and Antimalarial Agents