Synthesis, cytotoxic evaluation and target identification of thieno[2,3- d ]pyrimidine derivatives with a dithiocarbamate side chain at C2 position

Yang, Chao-Rui; Peng, Bin; Cao, Sheng‐Li; Ren, Ting-Ting; Jiang, Wei; Wang, Fucheng; Li, Youshan; Guo, Wang; Li, Zheng; Xu, Shibin; Liao, Ji; Wang, Hailong; Li, Jing; Xu, Xingzhi

doi:10.1016/j.ejmech.2018.05.028

Cited by 20 publications

(22 citation statements)

References 33 publications

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“…As compounds containing thieno[2,3-d]pyrimidine motif have been reported to possess cytotoxicity against cancer cell lines [20,29,30,31], we evaluated the antiproliferative activity of thieno[2,3-d]pyrimidin-4(3H)-one compounds synthesized herein, against several human cancer cells, as well as human normal liver cells (HL-7702). The cancer cells used in the research include human non-small cell lung cancer cells A549, PC-9, human prostate cancer cell PC-3, and human breast cancer cell line MCF-7.…”

Section: Resultsmentioning

confidence: 99%

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Synthesis of Novel Analogs of Thieno[2,3-d] Pyrimidin-4(3H)-ones as Selective Inhibitors of Cancer Cell Growth

et al. 2019

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New 2,3-disubstituted thieno[2,3-d]pyrimidin-4(3H)-ones were synthesized via a one-pot reaction from 2H-thieno[2,3-d] [1,3]oxazine-2,4(1H)-diones, aromatic aldehydes, and benzylamine or 4-hydroxylbezylamine. The obtained compounds were tested in vitro for cancer cell growth inhibition. Compound 19 can inhibit all four types of tested cancer cells, i.e., MCF-7, A549, PC-9, and PC-3 cells. Most of the compounds inhibited the proliferation of A549 and MCF-7 cells. Compound 15 exhibited the strongest anti-proliferative effect against A549 cell lines with IC50 values of 0.94 μM, and with no toxicity to normal human liver cells. Its potency was further proved by cell clone formation assay, Hoechst 33258 staining, and evaluation on the effects of apoptosis-related proteins.

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Section: Resultsmentioning

confidence: 99%

“…Recently reported representative compounds with the thieno[2,3- d ] pyrimidine motif as potent anti-cancer agents. [20,29,30,31]. …”

Section: Figures Scheme and Tablementioning

confidence: 99%

Synthesis of Novel Analogs of Thieno[2,3-d] Pyrimidin-4(3H)-ones as Selective Inhibitors of Cancer Cell Growth

et al. 2019

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“…The identification of proteins by mass spectrometry was performed as previously described. 49 4.2.8. Biotin−Streptavidin Pulldown Assay.…”

Section: Identification Of Compound 5amentioning

confidence: 99%

A 1,2,3-Triazole Derivative of Quinazoline Exhibits Antitumor Activity by Tethering RNF168 to SQSTM1/P62

et al. 2022

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Quinazoline and its derivatives have drawn much attention in the development of potential antitumor agents. Here, we synthesized a series of 1,2,3-triazole derivatives of quinazoline at the C6 position and evaluated for their cytotoxic activity in various human cancer cell lines. We found that compound 5a was the most cytotoxic to HCT-116 cells (IC50, 0.36 μM). Target profiling found that 5a directly binds to both the autophagy-associated protein SQSTM1/P62 and the E3 ligase RNF168, promoting their interaction. Consistently, 5a treatment induces a decrease in RNF168-mediated H2A ubiquitination and compromises homologous recombination-mediated DNA repair, thus increasing the sensitivity of HCT-116 to X-ray radiation. Moreover, 5a suppressed xenografted tumor growth in mice in a dose-dependent manner. Taken together, the 1,2,3-triazole derivative of quinazoline 5a may serve as a novel compound for tumor therapy based on its role in promoting a P62/RNF168 interaction.

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“…In this review, we have presented and discussed the different applications of these compounds as potential antiparasitic compounds, more specifically as antitrypanosomatids-drugs against Chagas disease, leishmaniasis, and African trypanosomiasis. It is also important to note that some of these compounds have already been validated for their specific pharmacological targets in in vitro models [84,85,86,87,88,89,90,91,92,93].…”

Section: Final Considerations and Expectationsmentioning

confidence: 99%

Application of Dithiocarbamates as Potential New Antitrypanosomatids-Drugs: Approach Chemistry, Functional and Biological

et al. 2019

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Dithiocarbamates represent a class of compounds that were evaluated in different biomedical applications because of their chemical versatility. For this reason, several pharmacological activities have already been attributed to these compounds, such as antiparasitic, antiviral, antifungal activities, among others. Therefore, compounds that are based on dithiocarbamates have been evaluated in different in vivo and in vitro models as potential new antimicrobials. Thus, the purpose of this review is to present the possibilities of using dithiocarbamate compounds as potential new antitrypanosomatids-drugs, which could be used for the pharmacological control of Chagas disease, leishmaniasis, and African trypanosomiasis.

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Synthesis, cytotoxic evaluation and target identification of thieno[2,3- d ]pyrimidine derivatives with a dithiocarbamate side chain at C2 position

Cited by 20 publications

References 33 publications

Synthesis of Novel Analogs of Thieno[2,3-d] Pyrimidin-4(3H)-ones as Selective Inhibitors of Cancer Cell Growth

Synthesis of Novel Analogs of Thieno[2,3-d] Pyrimidin-4(3H)-ones as Selective Inhibitors of Cancer Cell Growth

A 1,2,3-Triazole Derivative of Quinazoline Exhibits Antitumor Activity by Tethering RNF168 to SQSTM1/P62

Application of Dithiocarbamates as Potential New Antitrypanosomatids-Drugs: Approach Chemistry, Functional and Biological

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