Identification of thiazolo[5,4-d]pyrimidine derivatives as potent antiproliferative agents through the drug repurposing strategy

Li, Zhonghua; Zhang, Ji; Liu, Xue-Qi; Geng, Pengfei; Ma, Junxia; Wang, Bo; Zhao, Tao-Qian; Zhao, Bing; Wei, Hao-Ming; Wang, Chao; Fu, Dong-Jun

doi:10.1016/j.ejmech.2017.04.056

Cited by 32 publications

(11 citation statements)

References 24 publications

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“…1). The members of the Bcl-2 family are the main regulators of apoptosis due to their abili ty to activate caspases and release cytochrome c from mitochondria [4]. In complex with cytochrome c and the pro-apoptotic protein APAF1, caspase 9 forms a cell destructive machine called the apoptosome.…”

Section: Resultsmentioning

confidence: 99%

“…Antifungal, antimicrobial, anticonvulsant, and antiproliferative activities have been also reported for thiazoles [1,3,4]. Li et al demonstrated that thiazolo [5,4-d]pyrimidine (5-(benzylthio)-7-morpholino-N-phenylthiazolo [5,4d]pyrimidin-2-amine) possesses growth inhibition effects towards human gastric cancer MGC803, gas-tric carcinoma HGC27, and lung cancer H1650 cells [4]. The pyridyl-thiazoles possess antiproliferative activity for human acute T lymphocyte leukemia Jurkat and colorectal HT-29 cells [5].…”

mentioning

confidence: 95%

“…As potential anticancer agents, heterocyclic compounds have been synthesized and their activity has been investigated [1][2][3][4][5]. Antifungal, antimicrobial, anticonvulsant, and antiproliferative activities have been also reported for thiazoles [1,3,4]. Li et al demonstrated that thiazolo [5,4-d]pyrimidine (5-(benzylthio)-7-morpholino-N-phenylthiazolo [5,4d]pyrimidin-2-amine) possesses growth inhibition effects towards human gastric cancer MGC803, gas-tric carcinoma HGC27, and lung cancer H1650 cells [4].…”

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confidence: 99%

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Apoptosis induction in human leukemia cells by novel 2-amino-5-benzylthiazole derivatives

Finiuk¹,

Ivasechko²,

Klyuchivska³

et al. 2019

Ukr.Biochem.J

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Section: Resultsmentioning

confidence: 99%

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confidence: 95%

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confidence: 99%

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Apoptosis induction in human leukemia cells by novel 2-amino-5-benzylthiazole derivatives

Finiuk¹,

Ivasechko²,

Klyuchivska³

et al. 2019

Ukr.Biochem.J

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“…An increased level of the cleaved form of PARP1 was detected for mag.SLPs, SLPs, IO-OA, and IO particles, although most of PARP1 protein remained uncleaved. Typically, DNA breaks induce poly(ADP-ribosyl)ation via activation of poly(ADP-ribose) polymerase (PARP) (Zhang and Xu, 2000;Brustmann, 2007;Li Z. H. et al, 2017), which causes a depletion of NAD+ and ATP, resulting in the induction of necrosis (Herceg and Wang, 1999). However, point mutation in the cleavage site of PARP, which leads to its resistance to caspases, accelerated cell death induced by the tumor necrosis factor alpha.…”

Section: Discussionmentioning

confidence: 99%

Magnetic Temperature-Sensitive Solid-Lipid Particles for Targeting and Killing Tumor Cells

et al. 2020

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Magnetic and temperature-sensitive solid lipid particles (mag. SLPs) were prepared in the presence of oleic acid-coated iron oxide (IO-OA) nanoparticles with 1-tetradecanol and poly(ethylene oxide)-block-poly(ε-caprolactone) as lipid and stabilizing surfactant-like agents, respectively. The particles, typically ∼850 nm in hydrodynamic size, showed heat dissipation under the applied alternating magnetic field. Cytotoxic activity of the mag.SLPs, non-magnetic SLPs, and iron oxide nanoparticles was compared concerning the mammalian cancer cell lines and their drug-resistant counterparts using trypan blue exclusion test and MTT assay. The mag.SLPs exhibited dose-dependent cytotoxicity against human leukemia cell lines growing in suspension (Jurkat and HL-60/wt), as well as the doxorubicin (Dox)-and vincristine-resistant HL-60 sublines. The mag.SLPs showed higher cytotoxicity toward drug-resistant sublines as compared to Dox. The human glioblastoma cell line U251 growing in a monolayer culture was also sensitive to mag.SLPs cytotoxicity. Staining of U251 cells with the fluorescent dyes Hoechst 33342 and propidium iodide (PI) revealed that mag.SLPs treatment resulted in an increased number of cells with condensed chromatin and/or fragmented nuclei as well as with blebbing of the plasma membranes. While the Hoechst 33342 staining of cell suggested the pro-apoptotic activity of the particles, the PI staining indicated the pro-necrotic changes in the target cells. These conclusions were confirmed by Western blot analysis of apoptosis-related proteins, study of DNA fragmentation (DNA laddering due to the inter-nucleosomal cleavage and DNA comets due to single strand breaks), as well as by FACS analysis of the patterns of cell cycle distribution (pre-G1 phase) and Annexin V/PI staining of the treated Jurkat cells. The induction of apoptosis or necrosis by the particles used to treat Jurkat cells depended on the dose of the particles. Production of the reactive oxygen species (ROS) was proposed as a potential mechanism of mag.SLPs-induced cytotoxicity. Accordingly, hydrogen peroxide and superoxide radical Ś więtek et al.Magnetic Solid-Lipid Particles levels in mag.SLPs-treated Jurkat leukemic cells were increased by ∼20-40 and ∼70%, respectively. In contrast, the non-magnetic SLPs and neat iron oxides did not influence ROS levels significantly. Thus, the developed mag.SLPs can be used for effective killing of human tumor cells, including drug-resistant ones.

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“…They exhibited anticancer [1][2][3][4][5], antioxidant [6][7][8], antifungal [9,10], and antibacterial activities [11][12][13][14]. Furthermore, thiazolopyrimidine derivatives were considered as potent cytotoxic, analgesic, and antifungal agents [24][25][26]. Furthermore, thiazolopyrimidine derivatives were considered as potent cytotoxic, analgesic, and antifungal agents [24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Some Novel Thiazolo[3,2‐a]pyrimidine and Pyrimido[2,1‐b][1,3]thiazine Derivatives and their Antimicrobial Evaluation

Behalo

2018

Journal of Heterocyclic Chem

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A 2‐(2‐Mercapto‐4‐(4‐phenoxyphenyl)‐6‐(thiophen‐2‐yl)‐1,6‐dihydropyrimidin‐5‐yl) acetic acid was used as a reactive key precursor to design various pyrimidine derivatives such as thiazolo[3,2‐a]pyrimidines and pyrimido[2,1‐b][1,3]thiazines. The chemical structures of the newly synthesized products were confirmed by their elemental analyses and spectral data (IR, 1H NMR, 13C NMR, and mass spectra). The antibacterial and antifungal activities of some of the synthesized products were also evaluated, and it was found that compounds 3, 5, 9, and 11 exhibited potent activity against tested microorganisms in comparison with standard drugs.

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Identification of thiazolo[5,4-d]pyrimidine derivatives as potent antiproliferative agents through the drug repurposing strategy

Cited by 32 publications

References 24 publications

Apoptosis induction in human leukemia cells by novel 2-amino-5-benzylthiazole derivatives

Apoptosis induction in human leukemia cells by novel 2-amino-5-benzylthiazole derivatives

Magnetic Temperature-Sensitive Solid-Lipid Particles for Targeting and Killing Tumor Cells

Synthesis of Some Novel Thiazolo[3,2‐a]pyrimidine and Pyrimido[2,1‐b][1,3]thiazine Derivatives and their Antimicrobial Evaluation

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