Design, synthesis and biological evaluation of novel C-29 carbamate celastrol derivatives as potent and selective cytotoxic compounds

Figueiredo, Sandra A. C.; Salvador, Jorge A. R.; Cortés, Roberto; Cascante, Marta

doi:10.1016/j.ejmech.2017.08.058

Cited by 26 publications

(18 citation statements)

References 47 publications

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“…To evaluate the cytotoxic activities of synthesized analogues, the antiproliferative activities of 2a – 2h were screened in a MTT assay in three human cancer cell lines: human non‐small cell lung cancer (A549), HeLa Cells, and human hepatoma cells (HepG‐2). In general, the cells were seeded in 96‐well culture plates and incubated overnight at 37 °C in a 5% CO 2 incubator.…”

Section: Methodsmentioning

confidence: 99%

“…Tang designed and synthesized a new class of C(6)‐indole substituted celastrol analogues and biological evaluation of some title compounds displayed better cytotoxic activities. Tang , Wang , Shan , Zhang , and Figueiredo ] also designed and synthesized a series of celastrol derivatives by modifying the C(29)‐carboxylic acid group and C(3)‐hydroxy group, and the relation tests of anticancer activities were progressed to explore the potential anticancer agents. Unfortunately, although much effort has been made to modify the structure of celastrol, the desired analogues of celastrol are far from being completely explored.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and Biological Evaluation of a Series of Novel Celastrol Derivatives with Amino Acid Chain

Pang

Luo

Liu

et al. 2018

Chemistry & Biodiversity

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The synthesis of celastrol analogues containing amino acid ester at the C(29) position and their evaluation for cytotoxic activities in vitro were reported. The MTT test showed that a set of derivatives with lower IC values than that of the positive control group cisplatin and the parent compound celastrol, which exhibited greater antiproliferative activities. The most potent title compounds 2a and 2e exhibited cytotoxic activities in vitro against HeLa and A549 cell lines with IC values of 0.371 and 0.237 μm, 0.235 and 0.109 μm, respectively. The apoptosis assay demonstrated that 2a and 2e can induces of A549 cell apoptosis in low concentrations. These results showed that 2a and 2e may be promising for further research as antitumor agents.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of a Series of Novel Celastrol Derivatives with Amino Acid Chain

Pang

Luo

Liu

et al. 2018

Chemistry & Biodiversity

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“…Carbamates, which are closely related to amides and ureas, were applied in drug design to improve metabolic stability and bioactivity . However, antibacterial agents with the carbamate unit as the pharmacophore are rarely reported .…”

Section: Introductionmentioning

confidence: 99%

Exploration of (3‐benzyl‐5‐hydroxyphenyl)carbamates as new antibacterial agents against Gram‐positive bacteria

Liang

Cheng

Wang

et al. 2020

Archiv der Pharmazie

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A series of (3‐benzyl‐5‐hydroxyphenyl)carbamates were evaluated as new antibacterial agents. Several compounds showed potent inhibitory activity against sensitive and drug‐resistant Gram‐positive bacteria. The compounds are ineffective against all tested Gram‐negative bacteria. The structure of the ester group exerted a profound effect on antibacterial activity. 4,4‐Dimethylcyclohexanyl carbamate 6h exhibited the most potent inhibitory activity against the standard and clinically isolated Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecalis (minimum inhibitory concentration = 4–8 µg/ml) strains. The preliminary experimental evidence indicated that these carbamates target the bacterial cell wall and share a similar mechanism of action with vancomycin.

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“…Carbamate derivatives (e.g., the steroid skeleton) have aroused scientific interest over the years for their antitumor activities [29,30,31,32,33]. This is because carbamate moiety can form extensive hydrophobic and hydrogen bonding interactions with binding sites.…”

Section: Introductionmentioning

confidence: 99%

Exploring New Structural Features of the 18β-Glycyrrhetinic Acid Scaffold for the Inhibition of Anaplastic Lymphoma Kinase

et al. 2019

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Novel 18β-glycyrrhetinic acid derivatives possessing a carbamate moiety and structurally similar ester derivatives were developed and evaluated for their efficacy as antitumor inhibitors. In the cellular assays, most of the N-substituted carbamate derivatives at the C3-position exhibited potent activities. The results of SAR investigation revealed that the introduction of the morpholine group at the C30-COOH led to a significant loss of the inhibitory potency. Among the ester derivatives, the ester group at C3-position also determined a noticeable reduction in the efficacy. Compound 3j exhibited the most prominent antiproliferative activity against six human cancer cells (A549, HT29, HepG2, MCF-7, PC-3, and Karpas299). Furthermore, compound 3j exerted a moderate inhibiting effect on the ALK. The results of molecular docking analyses suggested that it could bind well to the active site of the receptor ALK, which was consistent with the biological data. These results might inspire further structural optimization of 18β-glycyrrhetinic acid aiming at the development of potent antitumor agents. The structures 4d, 4g, 4h, 4j, and 4n were studied by X-ray crystallographic analyses.

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Design, synthesis and biological evaluation of novel C-29 carbamate celastrol derivatives as potent and selective cytotoxic compounds

Cited by 26 publications

References 47 publications

Synthesis and Biological Evaluation of a Series of Novel Celastrol Derivatives with Amino Acid Chain

Synthesis and Biological Evaluation of a Series of Novel Celastrol Derivatives with Amino Acid Chain

Exploration of (3‐benzyl‐5‐hydroxyphenyl)carbamates as new antibacterial agents against Gram‐positive bacteria

Exploring New Structural Features of the 18β-Glycyrrhetinic Acid Scaffold for the Inhibition of Anaplastic Lymphoma Kinase

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