Recent advances in the discovery of small molecules targeting glioblastoma

Fernandes, Guilherme Felipe dos Santos; Fernandes, Barbara Colatto; Valente, Valéria; Santos, Jean Leandro dos

doi:10.1016/j.ejmech.2018.12.033

Cited by 19 publications

(20 citation statements)

References 137 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In this study, Actinomycins D (15) and V(16) showed values of IC 50 of 1.01-10.06 µM and 0.42 to 1.80 µM, respectively. From the Fradimicins, two compounds were identified and isolated showing potent activity against glioma cells, but Fradimicin(18) showed an IC 50 of 0.47 µM and induced apoptosis and necrosis of HCT-15, SW620, C6 cells and blocked HCT-15 cells in the phase G0/G1. Finally, from Streptoglutarimides, only two compounds were also isolated, with compound 21 showing an IC 50 value of 0.05-0.22 µM and revealing more potent antiproliferative activity against glioma cells than compound 20.…”

mentioning

confidence: 99%

Small Molecules of Marine Origin as Potential Anti-Glioma Agents

et al. 2021

View full text Add to dashboard Cite

Marine organisms are able to produce a plethora of small molecules with novel chemical structures and potent biological properties, being a fertile source for discovery of pharmacologically active compounds, already with several marine-derived agents approved as drugs. Glioma is classified by the WHO as the most common and aggressive form of tumor on CNS. Currently, Temozolomide is the only chemotherapeutic option approved by the FDA even though having some limitations. This review presents, for the first time, a comprehensive overview of marine compounds described as anti-glioma agents in the last decade. Nearly fifty compounds were compiled in this document and organized accordingly to their marine sources. Highlights on the mechanism of action and ADME properties were included. Some of these marine compounds could be promising leads for the discovery of new therapeutic alternatives for glioma treatment.

show abstract

mentioning

confidence: 99%

Small Molecules of Marine Origin as Potential Anti-Glioma Agents

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Till now, most curative chemotherapeutic agents with better BBB/BBTB passage for GBM therapies are temozolomide (TMZ) (Reyderman et al., 2004; Portnow et al., 2009; Goldwirt et al., 2014), lomustine (CCNU) (Taal et al., 2014), procarbazine (Sekine et al., 2000; Weidle et al., 2015), and carboplatin (Jacobs et al., 2010; Weidle et al., 2015) (Figure 2). TMZ is to date the most frequently used and the FDA-approved chemotherapeutic agent for GBM treatment (Fernandes et al., 2019). In human brain adjacent to tumor, TMZ displayed a brain/plasma ratio of 18% and a cerebrospinal fluid (CSF)/plasma ratio of 20–40% (Portnow et al., 2009; Goldwirt et al., 2013).…”

Section: Delivery Of Small-molecule Chemotherapeutic Agents Across Thmentioning

confidence: 99%

“…Based on the medicinal chemistry strategies in the development of small molecules for GBM chemotherapy, some anti-GBM drug candidate compounds derived from pyrimidines, quinolines, indazoles, and triazines have been identified in the last decade (Fernandes et al., 2019). These compounds have been demonstrated to effectively inhibit the GBM tumor growth in a panel of models in vivo , indicating their better BBB/BBTB permeable potential.…”

Section: Delivery Of Small-molecule Chemotherapeutic Agents Across Thmentioning

confidence: 99%

A comprehensive review in improving delivery of small-molecule chemotherapeutic agents overcoming the blood-brain/brain tumor barriers for glioblastoma treatment

Wang

et al. 2019

Drug Delivery

135

View full text Add to dashboard Cite

Glioblastoma (GBM) is the most common and lethal primary brain tumor which is highly resistant to conventional radiotherapy and chemotherapy, and cannot be effectively controlled by surgical resection. Due to inevitable recurrence of GBM, it remains essentially incurable with a median overall survival of less than 18 months after diagnosis. A great challenge in current therapies lies in the abrogated delivery of most of the chemotherapeutic agents to the tumor location in the presence of blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB). These protective barriers serve as a selectively permeable hurdle reducing the efficacy of anti-tumor drugs in GBM therapy. This work systematically gives a comprehensive review on: (i) the characteristics of the BBB and the BBTB, (ii) the influence of BBB/BBTB on drug delivery and the screening strategy of small-molecule chemotherapeutic agents with promising BBB/BBTB-permeable potential, (iii) the strategies to overcome the BBB/BBTB as well as the techniques which can lead to transient BBB/BBTB opening or disruption allowing for improving BBB/BBTB-penetration of drugs. It is hoped that this review provide practical guidance for the future development of small BBB/BBTB-permeable agents against GBM as well as approaches enhancing drug delivery across the BBB/BBTB to GBM.

show abstract

“…It is a fast-growing malignant tumor that arises from multiple cell types with neural stem-cell-like properties. Besides conventional therapy, current approaches such as small molecules and gene therapy are developed in recent years [2, 3]. New synthetic small molecules were discovered as promising anti-GBM agents [3].…”

Section: Introductionmentioning

confidence: 99%

“…Besides conventional therapy, current approaches such as small molecules and gene therapy are developed in recent years [2, 3]. New synthetic small molecules were discovered as promising anti-GBM agents [3]. Although with various treatments, patient outcomes remain between 12 and 15 months survival rate, and with five-year survival rates at only 10% [4].…”

Section: Introductionmentioning

confidence: 99%

Integrative analysis of DNA methylation and gene expression to identify key epigenetic genes in glioblastoma

Jia

Lin

Tang

et al. 2019

Aging

View full text Add to dashboard Cite

Glioblastoma (GBM) ranks the most common and aggressive primary brain malignant tumor worldwide. However, the survival rates of patients remain very poor. Therefore, molecular oncology of GBM are urgently needed. In this study, we performed an integrative analysis of DNA methylation and gene expression to identify key epigenetic genes in GBM. The methylation and gene expression of GBM patients in The Cancer Genome Atlas (TCGA) database were downloaded. After data preprocessing, we identified 4,881 differentially expressed genes (DEGs) between tumor and normal samples, including 1,111 upregulated and 3,770 downregulated genes. Then, we randomly separated all samples into training set (n = 69) and testing set (n = 69). We next obtained 11,269 survival-methylation sites by univariate and multivariate Cox regression analyses. In the correlation analysis, we defined 198 low promoter methylation with high gene expression as epigenetically induced (EI) genes and 111 high promoter methylation with low gene expression as epigenetically suppressed (ES) genes. Key markers including C1orf61 and FAM50B were selected with a Pearson correlation coefficient greater than 0.75. Further, we chose the 20 CpG methylation sites of above two genes in unsupervised clustering analysis using the Euclidean distance. We found that the prognosis of the hypomethylated group was significantly better than that in the hypermethylated group (log-rank test p -value = 0.011). Based on the validation in the TCGA testing set and GEO dataset, we validated the prognostic value of our signature ( p -value = 0.02 in TCGA and 0.012 in GEO). In conclusion, our findings provided predictive and prognostic value as methylation-based biomarkers for the diagnosis and treatment of GBM.

show abstract

Recent advances in the discovery of small molecules targeting glioblastoma

Cited by 19 publications

References 137 publications

Small Molecules of Marine Origin as Potential Anti-Glioma Agents

Small Molecules of Marine Origin as Potential Anti-Glioma Agents

A comprehensive review in improving delivery of small-molecule chemotherapeutic agents overcoming the blood-brain/brain tumor barriers for glioblastoma treatment

Integrative analysis of DNA methylation and gene expression to identify key epigenetic genes in glioblastoma

Contact Info

Product

Resources

About