Design, synthesis and biological evaluation of [1,2,3]triazolo[4,5-d]pyrimidine derivatives possessing a hydrazone moiety as antiproliferative agents

Li, Zhonghua; Yang, Dongxiao; Geng, Pengfei; Zhang, Ji; Wei, Hao-Ming; Hu, Biao; Guo, Qin; Zhang, Xinhui; Guo, Wenge; Zhao, Bing; Yu, Bin; Ma, Liying

doi:10.1016/j.ejmech.2016.10.022

Cited by 67 publications

(17 citation statements)

References 34 publications

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“…The synthetic route of the title compounds is demonstrated in Scheme 1 . The starting chlorides 1 were prepared from 4,6-dihydroxy-2-mercaptopyrimidine within 6 steps according to the previously reported methods 14 , 15 , 16 . And the target compounds 3 – 24 were readily prepared in 70%–90% yields by reacting 1 with different amines 2 under alkaline conditions.…”

Section: Resultsmentioning

confidence: 99%

Discovery of [1,2,3]triazolo[4,5-d]pyrimidine derivatives as highly potent, selective, and cellularly active USP28 inhibitors

Liu

Zhao

et al. 2020

Acta Pharmaceutica Sinica B

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Ubiquitin specific peptidase 28 (USP28) is closely associated to the occurrence and development of various malignancies, and thus has been validated as a promising therapeutic target for cancer therapy. To date, only few USP28 inhibitors with moderate inhibitory activity have been reported, highly potent and selective USP28 inhibitors with new chemotypes remain to be discovered for pathologically investigating the roles of deubiquitinase. In this current study, we reported the synthesis and biological evaluation of new [1,2,3]triazolo[4,5- d ]pyrimidine derivatives as potent USP28 inhibitors. Especially, compound 19 potently inhibited USP28 (IC 50 = 1.10 ± 0.02 μmol/L, K d = 40 nmol/L), showing selectivity over USP7 and LSD1 (IC 50 > 100 μmol/L). Compound 19 was cellularly engaged to USP28 in gastric cancer cells. Compound 19 reversibly bound to USP28 and directly affected its protein levels, thus inhibiting the proliferation, cell cycle at S phase, and epithelial-mesenchymal transition (EMT) progression in gastric cancer cell lines. Docking studies were performed to rationalize the potency of compound 19 . Collectively, compound 19 could serve as a new tool compound for the development of new USP28 inhibitors for exploring the roles of deubiquitinase in cancers.

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Section: Resultsmentioning

confidence: 99%

Discovery of [1,2,3]triazolo[4,5-d]pyrimidine derivatives as highly potent, selective, and cellularly active USP28 inhibitors

Liu

Zhao

et al. 2020

Acta Pharmaceutica Sinica B

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“…The highest DMSO concentration of the medium (0.1%) did not have any substantial effect on the determined cellular functions. The MTT assay was prepared according to the previous method [ 26 , 27 , 28 ].…”

Section: Methodsmentioning

confidence: 99%

Design and Antiproliferative Evaluation of Novel Sulfanilamide Derivatives as Potential Tubulin Polymerization Inhibitors

Liu

Zhao

et al. 2017

Molecules

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A series of sulfanilamide-1,2,3-triazole hybrids were designed by a molecular hybridization strategy and evaluated for antiproliferative activity against three selected cancer cell lines (MGC-803, MCF-7 and PC-3). The detailed structure-activity relationships for these sulfanilamide-1,2,3-triazole hybrids were investigated. All these sulfanilamide-1,2,3-triazole hybrids exhibited moderate to potent activity against all cell lines. In particular 4-methyl-N-((1-(3-phenoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl)benzenesulfonamide (11f) showed the most potent inhibitory effect against PC-3 cells, with an IC50 value of 4.08 μM. Furthermore, the tubulin polymerization inhibitory activity in vitro of compound 11f was 2.41 μM. These sulfanilamide hybrids might serve as bioactive fragments for developing more potent antiproliferative agents.

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“…Hydrazones bearing pyrimidine moiety have proven potent inhibitor of L1196 M anaplastic lymphoma kinase and ROS1, non‐nucleoside reverse transcriptase (NNRT), cyclin D1‐cyclin‐dependent kinase 4, mammalian target of rapamycin inhibitor and also identified as antimicrobial and antiproliferative agents.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Anthelmintic and Antimicrobial Evaluation of New 2‐Arylidene‐1‐(4‐methyl‐6‐phenylpyrimidin‐2‐yl)hydrazines

Kamal

Kumar

et al. 2019

ChemistrySelect

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A series of eighteen novel 2‐arylidene‐1‐(4‐methyl‐6‐phenylpyrimidin‐2‐yl)hydrazine derivatives were synthesized by simple condensation of 2‐hydrazinyl‐4‐methyl‐6‐phenylpyrimidine with benzaldehyde derivatives with an anticipation to find new biochemical hydrazones. Detailed structural analyses were delineated by means of their IR, 1H NMR, 13C NMR, and HRMS analysis. In vitro antimicrobial evaluation was carried out against two gram‐positive bacteria (Bacillus subtilis MTCC 121 and Staphylococcus aureus MTCC 96) and two gram‐negative bacteria (Escherichia coli MTCC 1652 and Pseudomonas aeruginosa MTCC 741). In vitro anthelmintic evaluations were also carried against Indian earthworm Pheretima posthuma (Annelida) using albendazole as reference drug.

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Design, synthesis and biological evaluation of [1,2,3]triazolo[4,5-d]pyrimidine derivatives possessing a hydrazone moiety as antiproliferative agents

Cited by 67 publications

References 34 publications

Discovery of [1,2,3]triazolo[4,5-d]pyrimidine derivatives as highly potent, selective, and cellularly active USP28 inhibitors

Discovery of [1,2,3]triazolo[4,5-d]pyrimidine derivatives as highly potent, selective, and cellularly active USP28 inhibitors

Design and Antiproliferative Evaluation of Novel Sulfanilamide Derivatives as Potential Tubulin Polymerization Inhibitors

Synthesis, Anthelmintic and Antimicrobial Evaluation of New 2‐Arylidene‐1‐(4‐methyl‐6‐phenylpyrimidin‐2‐yl)hydrazines

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