4.7 Article

Discovery of semisynthetic celastrol derivatives exhibiting potent anti-ovarian cancer stem cell activity and STAT3 inhibition

相关参考文献

注意:仅列出部分参考文献,下载原文获取全部文献信息。
Article Chemistry, Medicinal

Synthesis and biological evaluation of celastrol derivatives as potential anti-glioma agents by activating RIP1/RIP3/MLKL pathway to induce necroptosis

Yao Feng et al.

Summary: In this study, a series of celastrol derivatives containing 1, 2, 3-triazole moiety were designed and synthesized, and their activities against glioma cells were evaluated. Compound 6i exhibited potent anti-glioma activity by inducing necroptosis through the RIP1/RIP3/MLKL pathway. Moreover, compound 6i showed acceptable BBB permeability in mice and inhibited glioma cell proliferation in an in vivo zebrafish xenograft model.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2022)

Article Biochemistry & Molecular Biology

Synthesis and biological evaluation of celastrol derivatives as potent antitumor agents with STAT3 inhibition

Shaohua Xu et al.

Summary: By synthesizing celastrol derivatives, we discovered an effective STAT3 inhibitor as a potential anti-tumor drug, which can suppress the activity of STAT3 and has anti-tumor effects.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY (2022)

Article Chemistry, Medicinal

Scaffold hopping of celastrol provides derivatives containing pepper ring, pyrazine and oxazole substructures as potent autophagy inducers against breast cancer cell line MCF-7

Yao Feng et al.

Summary: In this study, three series of celastrol derivatives were designed, synthesized, and evaluated for their antiproliferative activity. The results showed that compound 11i exhibited potent activity against breast cancer cells by inducing autophagy and regulating cell cycle-related proteins. Moreover, the inhibitory effect of compound 11i was also confirmed in a zebrafish xenograft model.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2022)

Article Chemistry, Medicinal

Discovery of Novel Celastrol-Imidazole Derivatives with Anticancer Activity In Vitro and In Vivo

Na Li et al.

Summary: By introducing substituted imidazoles, significant improvements in antiproliferation, covalent-binding ability, and Hsp90-Cdc37 inhibition were achieved compared to CEL. Compound 9, the most potent derivative, showed higher activity in inducing apoptosis and inhibiting tumor growth in vivo. This study provides support for the development of CEL and other Michael acceptors as antitumor agents.

JOURNAL OF MEDICINAL CHEMISTRY (2022)

Article Plant Sciences

Thiazolidinedione-Based Structure Modification of Celastrol Provides Thiazolidinedione-Conjugated Derivatives as Potent Agents against Non-Small-Cell Lung Cancer Cells through a Mitochondria-Mediated Apoptotic Pathway

Xuefeng Fu et al.

Summary: By modifying the structure of celastrol, compound 10b was developed and showed significant anti-cancer activity against A549 cell line. It induced apoptosis through regulating the expression of apoptosis-related proteins and activating the mitochondria-mediated apoptotic pathway.

JOURNAL OF NATURAL PRODUCTS (2022)

Article Plant Sciences

Design and Synthesis of Novel Celastrol Derivatives as Potential Anticancer Agents against Gastric Cancer Cells

Zhi-Chao Lei et al.

Summary: Gastric cancer is a common malignant disease, and finding novel agents for its treatment is urgent. In this study, pyrazole analogues were introduced to a natural product called celastrol, resulting in the synthesis of 24 new derivatives. Compound 21 exhibited the best antitumor activity against gastric cancer cells, mainly by increasing reactive oxygen species levels and inducing cell apoptosis.

JOURNAL OF NATURAL PRODUCTS (2022)

Article Oncology

Celastrol and Resveratrol Modulate SIRT Genes Expression and Exert Anticancer Activity in Colon Cancer Cells and Cancer Stem-like Cells

Helena Moreira et al.

Summary: The recovery rate in patients with metastatic colorectal cancer is low due to drug resistance and the presence of colorectal cancer stem cells (CSCs). Phytochemicals like -celastrol and resveratrol have shown promise in colon cancer therapy due to their low toxicity and ability to interact with various biological targets. This study investigates the anticancer mechanisms of these compounds against metastatic colon cancer cells and their capacity to eradicate CSCs.

CANCERS (2022)

Review Pharmacology & Pharmacy

Role of STAT3 signaling transduction pathways in cancer stem cell-associated chemoresistance

Po-Chang Shih et al.

Summary: Chemoresistance resulting from cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) leads to inconsistent chemotherapeutic efficacy. The presence of CSCs and EMT allows cancer cells to switch between differentiated and stem-like states, known as cellular plasticity. Phosphorylated signal transducer and activator of transcription 3 (pSTAT3) is increasingly recognized as a major factor in CSCs and EMT, with preclinical studies showing reversal of chemoresistance through STAT3 pathway inhibition. This review focuses on mechanisms involving STAT3 and its target genes in regulating EMT, and also discusses the status of clinical trials using STAT3 pathway inhibitors.

DRUG DISCOVERY TODAY (2021)

Article Oncology

Celastrol in cancer therapy: Recent developments, challenges and prospects

Hannah Ying Lim et al.

Summary: The review summarizes the potential and mechanisms of celastrol in cancer treatment, discusses the obstacles hindering its use in humans, and provides insights into future directions for research and development.

CANCER LETTERS (2021)

Article Medicine, Research & Experimental

Inhibition of breast cancer stem-like cells by a triterpenoid, ursolic acid, via activation of Wnt antagonist, sFRP4 and suppression of miRNA-499a-5p

Saurabh Mandal et al.

Summary: The study showed that ursolic acid can target breast cancer stem cells via Wnt by suppressing miR-499a-5p and upregulating the Wnt antagonist sFRP4, demonstrating significant anti-CSC ability.

LIFE SCIENCES (2021)

Article Chemistry, Medicinal

Synthesis, computational docking and biological evaluation of celastrol derivatives as dual inhibitors of SERCA and P-glycoprotein in cancer therapy

Paolo Coghi et al.

Summary: Celastrol-dipeptide derivatives exhibit high anti-proliferative activity and selectivity towards liver cancer cells, inducing apoptosis and inhibiting P-gp-mediated drug efflux. Compound 3 shows greater efficiency in inhibiting drug efflux compared to the inhibitor verapamil.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Chemistry, Medicinal

A Novel Anticancer Stem Cell Compound Derived from Pleuromutilin Induced Necroptosis of Melanoma Cells

Kun Zhang et al.

Summary: This study introduces a novel Pleuromutilin derivative, compound 38, which induces necroptosis in melanoma cancer cells and demonstrates promising anti-tumor effects in animal models. This compound also shows low toxicity and excellent pharmacokinetic properties, making it a potential candidate for anticancer drug development.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Oncology

Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Hyuna Sung et al.

Summary: The global cancer burden in 2020 saw an estimated 19.3 million new cancer cases and almost 10.0 million cancer deaths. Female breast cancer surpassed lung cancer as the most commonly diagnosed cancer, while lung cancer remained the leading cause of cancer death. These trends are expected to rise in 2040, with transitioning countries experiencing a larger increase compared to transitioned countries due to demographic changes and risk factors associated with globalization and a growing economy. Efforts to improve cancer prevention measures and provision of cancer care in transitioning countries will be crucial for global cancer control.

CA-A CANCER JOURNAL FOR CLINICIANS (2021)

Review Pharmacology & Pharmacy

Celastrol in metabolic diseases: Progress and application prospects

Shaohua Xu et al.

Summary: Celastrol, as an active ingredient derived from plants, has shown great potential in the treatment of metabolic diseases. Its anti-obesity effect is achieved through regulating various aspects, and it also shows effects on diseases like diabetes, atherosclerosis, and osteoporosis.

PHARMACOLOGICAL RESEARCH (2021)

Article Biochemistry & Molecular Biology

Reactive oxygen species produced by altered tumor metabolism impacts cancer stem cell maintenance

Kaysaw Tuy et al.

Summary: Controlling ROS levels is crucial for regulating tumor biology, especially within the CSC population. The role of ROS under hypoxia in the tumor microenvironment is significant. Metabolic shifts provide survival advantages while reducing damage from oxidative stress.

REDOX BIOLOGY (2021)

Article Biochemistry & Molecular Biology

Discovery of novel celastrol-triazole derivatives with Hsp90-Cdc37 disruption to induce tumor cell apoptosis

Na Li et al.

Summary: Compound 6, designed to enhance the disruption of Hsp90-Cdc37, showed enhanced anti-proliferative activity on cancer cell lines, inhibited the expression of key clients, and induced tumor cell apoptosis. The compound's increased activity may be attributed to its enhanced covalent binding with thiols and ability to arrest cells in the G0/G1 phase. Further exploration of compound 6 for cancer treatment is warranted.

BIOORGANIC CHEMISTRY (2021)

Article Chemistry, Medicinal

Design, synthesis of novel celastrol derivatives and study on their antitumor growth through HIF-1α pathway

Fan-Fan Shang et al.

Summary: Four derivatives of hypoxia-inducible factor-1 alpha (HIF-1 alpha), with modifications to the C-29 carboxyl group of celastrol, were synthesized and evaluated for their anticancer activities. Among the derivatives, compound C6 showed the best features, exhibiting strong HIF-1 alpha inhibitory activity, low cytotoxicity, and promising safety factor. In vivo experiments with C6 demonstrated good antitumor activity with minimal toxic effects, making it a promising agent for cancer treatment.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Plant Sciences

Synthesis and Biological Evaluation of Celastrol Derivatives with Improved Cytotoxic Selectivity and Antitumor Activities

Xiao-Long Hu et al.

Summary: In this study, 31 new celastrol derivatives were synthesized and evaluated for their ability to disrupt the Hsp90-Cdc37 interaction and inhibit cancer cell proliferation. Compound 4f showed the highest tumor cell selectivity, potent Hsp90-Cdc37 disruption activity, and antiproliferative effects, making it a promising candidate for the development of new cancer therapies. Further research demonstrated that 4f has strong antitumor activities in vitro and in vivo, with less toxicity compared to celastrol, suggesting its potential as a new cancer treatment option.

JOURNAL OF NATURAL PRODUCTS (2021)

Review Chemistry, Medicinal

Biosynthesis, total synthesis, structural modifications, bioactivity, and mechanism of action of the quinone-methide triterpenoid celastrol

Yun Lu et al.

Summary: Celastrol, a quinone-methide triterpenoid, has shown potential in anticancer, anti-inflammatory, and antiobesity activities. Studies on its chemical structure and biosynthesis have advanced, but its clinical applications are limited due to toxic effects. Structural modifications have been explored to improve its pharmacological properties for future research.

MEDICINAL RESEARCH REVIEWS (2021)

Review Chemistry, Medicinal

Celastrol: Progresses in structure-modifications, structure-activity relationships, pharmacology and toxicology

Wei Hou et al.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2020)

Article Biochemistry & Molecular Biology

Curcumin-Mediated Apoptotic Cell Death in Papillary Thyroid Cancer and Cancer Stem-Like Cells through Targeting of the JAK/STAT3 Signaling Pathway

Abdul Q. Khan et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

Article Cardiac & Cardiovascular Systems

Celastrol Attenuates Angiotensin II-Induced Cardiac Remodeling by Targeting STAT3

Shiju Ye et al.

CIRCULATION RESEARCH (2020)

Review Pharmacology & Pharmacy

Celastrol: A Review of Useful Strategies Overcoming its Limitation in Anticancer Application

Jinfeng Shi et al.

FRONTIERS IN PHARMACOLOGY (2020)

Review Chemistry, Multidisciplinary

Cancer stem cell-targeted bio-imaging and chemotherapeutic perspective

Jiyou Han et al.

CHEMICAL SOCIETY REVIEWS (2020)

Review Medicine, General & Internal

Treatment of epithelial ovarian cancer

Lindsay Kuroki et al.

BMJ-BRITISH MEDICAL JOURNAL (2020)

Review Oncology

STAT3 signaling in ovarian cancer: a potential therapeutic target

Renba Liang et al.

JOURNAL OF CANCER (2020)

Review Biochemistry & Molecular Biology

Targeting cancer stem cell pathways for cancer therapy

Liqun Yang et al.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2020)

Article Pharmacology & Pharmacy

Celastrol induce apoptosis of human multiple myeloma cells involving inhibition of proteasome activity

Yue-ling Zhong et al.

EUROPEAN JOURNAL OF PHARMACOLOGY (2019)

Article Chemistry, Medicinal

Synthesis and biological evaluation of celastrol derivatives as anti-ovarian cancer stem cell agents

Xiaojing Li et al.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2019)

Review Cell Biology

Ovarian cancer stem cell: A potential therapeutic target for overcoming multidrug resistance

Aynaz Mihanfar et al.

JOURNAL OF CELLULAR PHYSIOLOGY (2019)

Review Biochemistry & Molecular Biology

STAT3, stem cells, cancer stem cells and p63

Michaela Galoczova et al.

CELLULAR & MOLECULAR BIOLOGY LETTERS (2018)

Article Medicine, Research & Experimental

Phytochemicals, withaferin A and carnosol, overcome pancreatic cancer stem cells as c-Met inhibitors

Shima Aliebrahimi et al.

BIOMEDICINE & PHARMACOTHERAPY (2018)

Review Pharmacology & Pharmacy

Targeting molecular pathways in cancer stem cells by natural bioactive compounds

Danila Cianciosi et al.

PHARMACOLOGICAL RESEARCH (2018)

Article Chemistry, Medicinal

Synthesis and Discovery Novel Anti-Cancer Stem Cells Compounds Derived from the Natural Triterpenoic Acids

Xinhua Liu et al.

JOURNAL OF MEDICINAL CHEMISTRY (2018)

Review Oncology

Stem cell fate in cancer growth, progression and therapy resistance

Nikki K. Lytle et al.

NATURE REVIEWS CANCER (2018)

Article Chemistry, Medicinal

Novel celastrol derivatives with improved selectivity and enhanced antitumour activity: Design, synthesis and biological evaluation

Sandra A. C. Figueiredo et al.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2017)

Article Chemistry, Medicinal

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

Sandra A. C. Figueiredo et al.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2017)

Review Pharmacology & Pharmacy

Napabucasin: An Update on the First-in-Class Cancer Stemness Inhibitor

Joleen M. Hubbard et al.

Article Oncology

Aldehyde dehydrogenase 1A1 in stem cells and cancer

Hiroyuki Tomita et al.

ONCOTARGET (2016)

Article Chemistry, Multidisciplinary

Remarkable Stereospecific Conjugate Additions to the Hsp90 Inhibitor Celastrol

Lada Klaic et al.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2011)