Biological activity and interaction mechanism of the diketopiperazine derivatives as tubulin polymerization inhibitors

Tian, Zhenhua; Chu, Yanyan; Wang, Hui; Zhong, Lili; Li, Wenbao

doi:10.1039/c7ra12173c

Cited by 18 publications

(16 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Specifically, Plinabulin, a synthetic analog of the natural DKP product halimide from marine-derived Aspergillus sp. CNC-139, has entered phase-III clinical study for the treatment of non-small cell lung cancer [ 9 , 10 ]. In the course of our continuing investigation on marine fungi [ 11 , 12 ], a further chemical investigation was performed on Eurotium sp.…”

Section: Introductionmentioning

confidence: 99%

Eurotiumins A–E, Five New Alkaloids from the Marine-Derived Fungus Eurotium sp. SCSIO F452

et al. 2018

View full text Add to dashboard Cite

Three new prenylated indole 2,5-diketopiperazine alkaloids (1–3) with nine known ones (5–13), one new indole alkaloid (4), and one new bis-benzyl pyrimidine derivative (14) were isolated and characterized from the marine-derived fungus Eurotium sp. SCSIO F452. 1 and 2, occurring as a pair of diastereomers, both presented a hexahydropyrrolo[2,3-b]indole skeleton. Their chemical structures, including absolute configurations, were elucidated by 1D and 2D NMR, HRESIMS, quantum chemical calculations of electronic circular dichroism, and single crystal X-ray diffraction experiments. Most isolated compounds were screened for antioxidative potency. Compounds 3, 5, 6, 7, 9, 10, and 12 showed significant radical scavenging activities against DPPH with IC50 values of 13, 19, 4, 3, 24, 13, and 18 µM, respectively. Five new compounds were evaluated for cytotoxic activities.

show abstract

Section: Introductionmentioning

confidence: 99%

Eurotiumins A–E, Five New Alkaloids from the Marine-Derived Fungus Eurotium sp. SCSIO F452

et al. 2018

View full text Add to dashboard Cite

show abstract

“…was also reported to induce the apoptosis of human cervical cancer and chondrosarcoma cells via the mitochondrial pathway [ 7 ]. Hence, gliotoxins have been used as a immunosuppressive agent, tumor suppressor, pesticide, and fungicide [ 4 , 16 , 17 , 18 ]. The elevated GSH could promote the anticancer activity of gliotoxins.…”

Section: Discussionmentioning

confidence: 99%

“…A synthetic analog of the natural gliotoxin derivative produced by marine-derived Aspergillus sp. CNC-139, named as plinabulin, has entered phase III clinical study for the treatment of nonsmall cell lung cancer [ 4 ]. Gliotoxin has also been developed as an antifungal agent to prevent rice BLAST and banded sclerotial blight [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

De Novo Transcriptome Sequencing of the Deep-Sea-Derived Fungus Dichotomomyces cejpii and Analysis of Gliotoxin Biosynthesis Genes

Ye¹,

Zhang²,

Liu³

et al. 2018

IJMS

View full text Add to dashboard Cite

Gliotoxin, produced by fungi, is an epipolythiodioxopiperazine (ETP) toxin with bioactivities such as anti-liver fibrosis, antitumor, antifungus, antivirus, antioxidation, and immunoregulation. Recently, cytotoxic gliotoxins were isolated from a deep-sea-derived fungus, Dichotomomyces cejpii. However, the biosynthetic pathway for gliotoxins in D. cejpii remains unclear. In this study, the transcriptome of D. cejpii was sequenced using an Illumina Hiseq 2000. A total of 19,125 unigenes for D. cejpii were obtained from 9.73 GB of clean reads. Ten genes related to gliotoxin biosynthesis were annotated. The expression levels of gliotoxin-related genes were detected through quantitative real-time polymerase chain reaction (qRT-PCR). The GliG gene, encoding a glutathione S-transferase (DC-GST); GliI, encoding an aminotransferase (DC-AI); and GliO, encoding an aldehyde reductase (DC-AR), were cloned and expressed, purified, and characterized. The results suggested the important roles of DC-GST, DC-AT, and DC-AR in the biosynthesis of gliotoxins. Our study on the genes related to gliotoxin biosynthesis establishes a molecular foundation for the wider application of gliotoxins from D. cejpii in the biomedical industry in the future.

show abstract

“…Microtubules are tube-shaped protein polymers consisting of 13 protofilaments, which are in turn composed of heterodimers of α- and β-tubulin [3]. In addition to being a key component of the cytoskeleton, microtubules are associated with a variety of cellular processes, including maintenance of cell shape and motility, intracellular transportation, cell signaling, protein trafficking, and cell division and mitosis.…”

Section: Introductionmentioning

confidence: 99%

Deoxypodophyllotoxin Exerts Anti-Cancer Effects on Colorectal Cancer Cells Through Induction of Apoptosis and Suppression of Tumorigenesis

Gamage

Park

Yang

et al. 2019

IJMS

View full text Add to dashboard Cite

Deoxypodophyllotoxin (DPT) is a cyclolignan compound that exerts anti-cancer effects against various types of cancers. DPT induces apoptosis and inhibits the growth of breast, brain, prostate, gastric, lung, and cervical tumors. In this study, we sought to determine the effect of DPT on cell proliferation, apoptosis, motility, and tumorigenesis of three colorectal cancer (CRC) cell lines: HT29, DLD1, and Caco2. DPT inhibited the proliferation of these cells. Specifically, the compound-induced mitotic arrest in CRC cells by destabilizing microtubules and activating the mitochondrial apoptotic pathway via regulation of B-cell lymphoma 2 (Bcl-2) family proteins (increasing Bcl-2 associated X (BAX) and decreasing B-cell lymphoma-extra-large (Bcl-xL)) ultimately led to caspase-mediated apoptosis. In addition, DPT inhibited tumorigenesis in vitro, and in vivo skin xenograft experiments revealed that DPT significantly decreased tumor size and tumor weight. Taken together, our results suggest DPT to be a potent compound that is suitable for further exploration as a novel chemotherapeutic for human CRC.

show abstract

Biological activity and interaction mechanism of the diketopiperazine derivatives as tubulin polymerization inhibitors

Abstract: Microtubules are a favorable target for development of anticancer agents.

Cited by 18 publications

References 36 publications

Eurotiumins A–E, Five New Alkaloids from the Marine-Derived Fungus Eurotium sp. SCSIO F452

Eurotiumins A–E, Five New Alkaloids from the Marine-Derived Fungus Eurotium sp. SCSIO F452

De Novo Transcriptome Sequencing of the Deep-Sea-Derived Fungus Dichotomomyces cejpii and Analysis of Gliotoxin Biosynthesis Genes

Deoxypodophyllotoxin Exerts Anti-Cancer Effects on Colorectal Cancer Cells Through Induction of Apoptosis and Suppression of Tumorigenesis

Contact Info

Product

Resources

About