Novel anticancer hybrids from diazen-1-ium-1,2-diolate nitric oxide donor and ROS inducer plumbagin: Design, synthesis and biological evaluations

Bao, Na; Ou, Jinfeng; Li, Na; Zou, Pian; Sun, Jianbo

doi:10.1016/j.ejmech.2018.04.047

Cited by 15 publications

(4 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DNA damage will finally lead to apoptotic alternations including membrane structure damage and high permeability, which is characterized as shrinking cells. Breakdown of DNA stems from CME‐induced lipid peroxidation and its oxidative impairment on nucleotide (Bao et al., 2018). In the previous research, CME‐induced apoptosis is correlated with caspase‐3 activation (Lee et al., 2006) and genotoxic effect (Li et al., 2020); however, mechanism is still not validated.…”

Section: Discussionmentioning

confidence: 99%

Cordyceps militaris extract induces apoptosis and pyroptosis via caspase‐3/PARP/GSDME pathways in A549 cell line

Lai

et al. 2021

Food Science & Nutrition

View full text Add to dashboard Cite

Cordyceps militaris (CM) is traditionally used as dietary therapy for lung cancer patients in China. CM extract (CME) is hydrosoluble fraction of CM and extensively investigated. Caspase‐3‐involved cell death is considered as its major anticancer mechanism but inconclusive. Therefore, we explore its caspase‐3‐dependent programmed cell death nature (apoptosis and pyroptosis) and validate its caspase‐3‐dependent property in loss‐of‐function experiment. Component profile of CME is detected by High Performance Liquid Chromatography‐ quadrupole time‐of‐flight mass spectrometry (HPLC‐qTOF). Results show that CME causes pyroptosis‐featured cell bubbling and cell lysis and inhibits cell proliferation in A549 cell. CME induces chromatin condensing and makes PI+/annexin V+ staining in bubbling cells, indicating genotoxicity, apoptosis, and pyroptosis cell death are caused by CME. High concentration of CME (200 μg/ml) exerts G2/M and G0 cell cycles arresting and suppresses P53‐downstream proliferative proteins, including P53, P21, CDC25B, CyclinB1, Bcl‐2, and BCL2 associated agonist of cell death (BAD), but 1–100 μg/ml of CME show less effect on proteins above. Correspondingly, caspase‐3 activity and caspase‐3 downstream proteins including pyroptotic effector gasdermin‐E (GSDME) and apoptotic marker cleaved‐poly‐ADP‐ribose polymerase (PARP) are significantly promoted by CME. Moreover, regarding membrane pore formation in pyroptotic cell, expression of membrane GSDME (GSDME antibody conjugated with PE‐Cy7 for detection in flow cytometry) is remarkably increased by CME treatment. By contrast, other pyroptosis‐related proteins such as P2X7, NLRP3, GSDMD, and Caspase‐1 are not affected after CME treatment. Additionally, TET2 is unexpectedly raised by CME. In present of caspase‐3 inhibitor Ac‐DEVD‐CHO (Ac‐DC), CME‐induced cytotoxicity, cell bubbling, and genotoxicity are reduced, and CME‐induced upregulation of apoptosis (cleaved‐PARP‐1) and pyroptosis (GSDME‐NT) proteins are reversed. Lastly, 22 components are identified in HPLC‐qTOF experiment, and they are classified into trophism, neoadjuvant component, cytotoxic component, and cancer deterioration promoter according to previous references. Conclusively, CME causes caspase‐3‐dependent apoptosis and pyroptosis in A549 through caspase‐3/PARP and caspase‐3/GSDME pathways, and it provides basic insight into clinic application of CME for cancer patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Cordyceps militaris extract induces apoptosis and pyroptosis via caspase‐3/PARP/GSDME pathways in A549 cell line

Lai

et al. 2021

Food Science & Nutrition

View full text Add to dashboard Cite

show abstract

“… 1,4-Naphthoquinone hybrids with 4-aza-podophyllotoxin as reported by Yang et al [ 42 ] and with diazeniumdiolate scaffold by Bao et al [ 43 ]. …”

Section: Figurementioning

confidence: 95%

“…In the design of their compounds, Bao et al [ 43 ] started from the evidence that high levels of nitric oxide (NO) and ROS are pro-apoptotic signals in cancerous cells. The hybrids were derived by conjugation through a linker of the natural scaffold of the plumbagin acting as ROS inducer and that of diazeniumdiolates (NONOates) known to be NO donors.…”

Section: Design Synthesis and Biological Evaluation Of Antitumor Hybridsmentioning

confidence: 99%

Hybrid Molecules Containing Naphthoquinone and Quinolinedione Scaffolds as Antineoplastic Agents

et al. 2022

View full text Add to dashboard Cite

In recent decades, molecular hybridization has proven to be an efficient tool for obtaining new synthetic molecules to treat different diseases. Based on the core idea of covalently combining at least two pharmacophore fragments present in different drugs and/or bioactive molecules, the new hybrids have shown advantages when compared with the compounds of origin. Hybridization could be successfully applied to anticancer drug discovery, where efforts are underway to develop novel therapeutics which are safer and more effective than those currently in use. Molecules presenting naphthoquinone moieties are involved in redox processes and in other molecular mechanisms affecting cancer cells. Naphthoquinones have been shown to inhibit cancer cell growth and are considered privileged structures and useful templates in the design of hybrids. The present work aims at summarizing the current knowledge on antitumor hybrids built using 1,4- and 1,2-naphthoquinone (present in natural compounds as lawsone, napabucasin, plumbagin, lapachol, α-lapachone, and β -lapachone), and the related quinolone- and isoquinolinedione scaffolds reported in the literature up to 2021. In detail, the design and synthetic approaches adopted to produce the reported compounds are highlighted, the structural fragments considered in hybridization and their biological activities are described, and the structure–activity relationships and the computational analyses applied are underlined.

show abstract

“…Nitrosothiols can be degraded to generate NO under specific environmental stimuli and can also synergize with reactive oxygen species (ROS) to kill tumor cells . NONOates can spontaneously decompose into two molecules of NO in the body, and the circulation time in the body can reach more than 10 h, which can be used as a long-acting donor of NO . Different types of NO donors have different chemical reactivity and release characteristics due to their different chemical structures, and the diverse NO release mechanisms make them attractive in tumor therapy research.…”

Section: Introductionmentioning

confidence: 99%

Nitric Oxide and Tumors: From Small-Molecule Donor to Combination Therapy

Huang

Zhang

Luo

et al. 2022

ACS Biomater. Sci. Eng.

View full text Add to dashboard Cite

As an important endogenous signaling molecule, nitric oxide (NO) is involved in various physiological and pathological activities in living organisms. It is proved that NO plays a critical role in tumor therapy, while the extremely short half-life and nonspecific distribution of NO greatly limit its further clinical applications. Thus, the past few decades have witnessed the progress made in conquering these shortcomings, including developing innovative NO donors, especially smart and multimodal nanoplatforms. These platforms can precisely control the spatiotemporal distribution of therapeutic agents in the organism, which make big differences in tumor treatment. Here current NO therapeutic mechanisms for cancer, NO donors from small molecules to smart-responsive nanodrug delivery platforms, and NObased combination therapy are comprehensively reviewed, emphasizing outstanding breakthroughs in these fields and hoping to bring new insights into NO-based tumor treatments.

show abstract

Novel anticancer hybrids from diazen-1-ium-1,2-diolate nitric oxide donor and ROS inducer plumbagin: Design, synthesis and biological evaluations

Cited by 15 publications

References 25 publications

Cordyceps militaris extract induces apoptosis and pyroptosis via caspase‐3/PARP/GSDME pathways in A549 cell line

Cordyceps militaris extract induces apoptosis and pyroptosis via caspase‐3/PARP/GSDME pathways in A549 cell line

Hybrid Molecules Containing Naphthoquinone and Quinolinedione Scaffolds as Antineoplastic Agents

Nitric Oxide and Tumors: From Small-Molecule Donor to Combination Therapy

Contact Info

Product

Resources

About