Discovery of 5,6-diaryl-1,2,4-triazines hybrids as potential apoptosis inducers

Fu, Dong-Jun; Song, Jian; Hou, Yuhui; Zhao, Ruo; Li, Jiahuan; Mao, Ruo-Wang; Yang, Jiajia; Li, Ping; Zi, Xiaolin; Li, Zhonghua; Zhang, Qingqing; Wang, Feiyan; Zhang, Sai‐Yang; Zhang, Yanbing; Liu, Hong‐Min

doi:10.1016/j.ejmech.2017.07.011

Cited by 35 publications

(11 citation statements)

References 36 publications

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“…Bioisosterism is a useful strategy in rational drug design to improve pharmacodynamic or pharmacokinetic properties of lead compounds 20 . In order to optimise the reported colchicine site tubulin inhibitor 4 and discovery more potently anticancer agents [21][22][23][24][25] , benzothiazole was used as a bioisostere of the benzoxazole in the lead structure. Herein, we synthesised a variety of benzothiazole derivatives based on the lead compound 4 by the bioisosterism approach.…”

Section: Introductionmentioning

confidence: 99%

Antiproliferative benzothiazoles incorporating a trimethoxyphenyl scaffold as novel colchicine site tubulin polymerisation inhibitors

Liu

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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Tubulin polymerisation inhibitors exhibited an important role in the treatment of patients with prostate cancer. Herein, we reported the medicinal chemistry efforts leading to a new series of benzothiazoles by a bioisosterism approach. Biological testing revealed that compound 12a could significantly inhibit in vitro tubulin polymerisation of a concentration dependent manner, with an IC 50 value of 2.87 lM. Immunofluorescence and EBI competition assay investigated that compound 12a effectively inhibited tubulin polymerisation and directly bound to the colchicine-binding site of b-tubulin in PC3 cells. Docking analysis showed that 12a formed hydrogen bonds with residues Tyr357, Ala247 and Val353 of tubulin. Importantly, it displayed the promising antiproliferative ability against C42B, LNCAP, 22RV1 and PC3 cells with IC 50 values of 2.81 lM, 4.31 lM, 2.13 lM and 2.04 lM, respectively. In summary, compound 12a was a novel colchicine site tubulin polymerisation inhibitor with potential to treat prostate cancer. A novel colchicine site tubulin polymer ization inhibitor Time/minutesFluorescence intensity

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Section: Introductionmentioning

confidence: 99%

Antiproliferative benzothiazoles incorporating a trimethoxyphenyl scaffold as novel colchicine site tubulin polymerisation inhibitors

Liu

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…In addition it was indicated that alkylating activity increase with the number of 2-chloroethylamino groups [31]. It is interesting, that 1,3,5-triazine can modulate the functions: HIV-1 reverse transcriptase, estrogen receptor β (ΕRβ), glutathione S-transferase [38, 40]. 1,3,5-triazines with 2-chloroethylamino fragment can inhibit DNA replication, cell cycle arrest, induce of apoptosis and inhibit of cancer cells growth [31].…”

Section: Discussionmentioning

confidence: 99%

“…This characteristic types of cell death, are discussed in our previous paper [35]. Program cell death (PCD), also termed type 1 PCD, plays an important role in development of tissue homeostasis, degenerative diseases and cancer [40]. Apoptosis is a complex and multi-stage process.…”

Section: Discussionmentioning

confidence: 99%

The cellular effects of novel triazine nitrogen mustards in glioblastoma LBC3, LN-18 and LN-229 cell lines

et al. 2019

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Summary1,3,5-triazine is an important heterocyclic skeleton for mono, two or three 2-chloroethylamine groups. The study presented here provides novel information on cellular effects of 1,3,5-triazine with mono, two or three 2-chloroethylamine groups in glioblastoma LBC3, LN-18 and LN-229 cell lines. In our study, the most cytotoxic effect was observed in 1,3,5-triazine with three 2-chloroethylamine groups (12f compound). It has been demonstrated that 12f induce time- and dose-dependent cytotoxicity in all investigated glioma cell lines. Apart from that in glioblastoma cells, treated with 12f compound, we noticed strong induction of apoptosis. In conclusion, this research provides novel information concerning cellular effects of apoptosis in LBC3, LN-18 and LN-229 cell lines. Moreover, we suggest that 12f compound may be a candidate for further evaluation as an effective chemotherapeutic agent for human glioblastoma cells.

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“…All operations were carried out in accordance with the requirements of the cell cycle detection kit (Beyotime Biotechnology, Shanghai, China). The samples were analyzed by flow cytometer, and the data were analyzed by using the ModFit LT software (Verity Software House, Topsham, ME, USA) [59].…”

Section: Methodsmentioning

confidence: 99%

Essential Oil from Pinus Koraiensis Pinecones Inhibits Gastric Cancer Cells via the HIPPO/YAP Signaling Pathway

et al. 2019

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Pinecone is a traditional folk herb, which has been used in China for many years. In this paper, the essential oil from Pinus koraiensis pinecones (PEO) was obtained by hydrodistillation and 41 compounds were identified by gas chromatography–mass spectrometry (GC-MS), mainly including α-Pinene (40.91%), Limonene (24.82%), and β-Pinene (7.04%). The purpose of this study was to investigate the anti-tumor activity of PEO on MGC-803 cells and its mechanism. Anti-tumor experiments in vitro showed PEO could significantly inhibit the proliferation and migration of MGC-803 cells, and it also could arrest the cell cycle in the G2/M phase, decrease the mitochondrial membrane potential, and induce apoptosis. Finally, the effects of PEO on genes expression on MGC-803 cells were analyzed by RNA sequencing, and results showed that after treatment with PEO, 100 genes were up-regulated, and 57 genes were down-regulated. According to the KEGG pathway and GSEA, FAT4, STK3, LATS2, YAP1, and AJUBA were down-regulated, which were related to HIPPO signaling pathway. Real-time PCR and western blot further confirmed the results of RNA sequencing. These results indicated that PEO may exert anti-tumor activity via the HIPPO/YAP signaling pathway. The anti-tumor mechanism of this oil can be further studied, which is important for the development of anti-tumor drugs.

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Discovery of 5,6-diaryl-1,2,4-triazines hybrids as potential apoptosis inducers

Cited by 35 publications

References 36 publications

Antiproliferative benzothiazoles incorporating a trimethoxyphenyl scaffold as novel colchicine site tubulin polymerisation inhibitors

Antiproliferative benzothiazoles incorporating a trimethoxyphenyl scaffold as novel colchicine site tubulin polymerisation inhibitors

The cellular effects of novel triazine nitrogen mustards in glioblastoma LBC3, LN-18 and LN-229 cell lines

Essential Oil from Pinus Koraiensis Pinecones Inhibits Gastric Cancer Cells via the HIPPO/YAP Signaling Pathway

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