Synthesis and biological evaluation of novel N-substituted 1H-dibenzo[a,c]carbazole derivatives of dehydroabietic acid as potential antimicrobial agents

Aim. Rosin, the traditional Chinese medicine, is reported to be able to inhibit skin cancer cell lines. In this report, we investigate the inhibitory effect against HCC cells of QC2, the derivative of rosin's main components dehydroabietic acid. Methods. MTT assay was used to determine the cytotoxicity of QC2. Morphological changes were observed by time-lapse microscopy and transmission electron microscopy and the cytoskeleton changes were observed by laser-scanning confocal microscopy. Cytomembrane integrity and organelles damage were confirmed by detection of the reactive oxygen (ROS), lactate dehydrogenase (LDH), and mitochondrial membrane potential (Δψm). The underlying mechanism was manifested by Western blotting. The oncotic cell death was further confirmed by detection of oncosis related protein calpain. Results. Swelling cell type and destroyed cytoskeleton were observed in QC2-treated HCC cells. Organelle damage was visualized by transmission electron microscopy. The detection of ROS accumulation, increased LDH release, and decreased ATP and Δψm confirmed the cell death. The oncotic related protein calpain was found to increase time-dependently in QC2-treated HCC cells, while its inhibitor PD150606 attenuated the cytotoxicity. Conclusions. Dehydroabietic acid derivative QC2 activated oncosis related protein calpain to induce the damage of cytomembrane and organelles which finally lead to oncosis in HCC cells.

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“…The synthetic route of compound QC2 is illustrated in Scheme 1 and the detailed methods could be found in the paper of Gu and coworkers [10]. …”

Section: Methodsmentioning

confidence: 99%

Dehydroabietic Acid Derivative QC2 Induces Oncosis in Hepatocellular Carcinoma Cells

Guang

Jiang

Wang

et al. 2014

BioMed Research International

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“…The reaction sequences employed for the synthesis of the target compounds (6a-h, 7a-h, 8a-h and 10a-j) was outlined in Schemes 1 and 2, according to the previous studies 35,40 . Initially, methyl 7oxo-dehydroabietate (3) was synthesised from the starting material dehydroabietic acid (1) through methyl esterification and oxidation by CrO 3 .…”

Section: Chemistrymentioning

confidence: 99%

“…Therefore, DAA has proved to be a promising starting material in search of derivatives with potent anticancer activities. In our previous studies, a series of N-substituted 1H-dibenzo[a,c]carbazole derivatives of DAA were synthesised, some of which showed notable antimicrobial activities 35 . Subsequently, in the in vitro cytotoxic assay, two compounds (QC2 and QC4) ( Figure 2) of these derivatives exhibited significant antiproliferative activity against hepatocarcinoma and gastric cancer cell lines with IC 50 values at low micromolar level.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and biological evaluation of novel N-(piperazin-1-yl)alkyl-1H-dibenzo[a,c]carbazole derivatives of dehydroabietic acid as potential MEK inhibitors

Chen

Qiao

Miao

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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In this paper, a series of novel 1H-dibenzo[a,c]carbazole derivatives of dehydroabietic acid bearing different N-(piperazin-1-yl)alkyl side chains were designed, synthesised and evaluated for their in vitro anticancer activities against three human hepatocarcinoma cell lines (SMMC-7721, HepG2 and Hep3B). Among them, compound 10g exhibited the most potent activity against three cancer cell lines with IC 50 values of 1.39 ± 0.13, 0.51 ± 0.09 and 0.73 ± 0.08 mM, respectively. In the kinase inhibition assay, compound 10g could significantly inhibit MEK1 kinase activity with IC 50 of 0.11 ± 0.02 mM, which was confirmed by western blot analysis and molecular docking study. In addition, compound 10g could elevate the intracellular ROS levels, decrease mitochondrial membrane potential, destroy the cell membrane integrity, and finally lead to the oncosis and apoptosis of HepG2 cells. Therefore, compound 10g could be a potent MEK inhibitor and a promising anticancer agent worthy of further investigations.

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“…力, 表现出许多独特的生物活性 [106,107] . 咔唑对硝基咪唑修饰得到的芳香胺乙基类化合物46 (图5)对枯草芽孢杆菌和金黄色葡萄球菌有较好的抑制效果(MIC= 0.90~1.90 µg/mL), 其中对枯草芽孢杆菌的抑制活性与临床药物阿米卡霉素(Amikacin)相当 [108] .…”

Section: 咔唑类化合物是一类具有刚性稠合结构的重要含氮芳杂环具有较大的共轭体系和较强的电子转移能unclassified

Researches and applications of nitroimidazole heterocycles in medicinal chemistry

Maddili

Tangadanchu

et al. 2018

Sci. Sin.-Chim

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Synthesis and biological evaluation of novel N-substituted 1H-dibenzo[a,c]carbazole derivatives of dehydroabietic acid as potential antimicrobial agents

Cited by 44 publications

References 37 publications

Dehydroabietic Acid Derivative QC2 Induces Oncosis in Hepatocellular Carcinoma Cells

Dehydroabietic Acid Derivative QC2 Induces Oncosis in Hepatocellular Carcinoma Cells

Synthesis and biological evaluation of novel N-(piperazin-1-yl)alkyl-1H-dibenzo[a,c]carbazole derivatives of dehydroabietic acid as potential MEK inhibitors

Researches and applications of nitroimidazole heterocycles in medicinal chemistry

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