Identification of novel 1,3-diaryl-1,2,4-triazole-capped histone deacetylase 6 inhibitors with potential anti-gastric cancer activity

Zhang, Xinhui; Kang, Huifang; Tao, Yuanyuan; Li, Yi-Han; Zhao, Jun-Ru; Ya-Gao,; Ma, Liying; Liu, Hong‐Min

doi:10.1016/j.ejmech.2021.113392

Cited by 19 publications

(10 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SAR study confirmed that compounds having two aromatic rings at N‐1 and C‐3 position of triazole showed improved potency. Results were validated using docking study and found that compound 46r exhibited excellent binding and affinity to HDAC6, proving the selectivity of this potent molecule for further development [70] …”

Section: Synthesis and Biological Evaluation Of Isolated/functionaliz...mentioning

confidence: 95%

“…Results were validated using docking study and found that compound 46r exhibited excellent binding and affinity to HDAC6, proving the selectivity of this potent molecule for further development. [70] Mohammed et al prepared 1,5-diaryl-N-aryl triazole-3-carboxamide 47 and derivatives from hydrazono-oxazolone derivatives and primary aromatic amines in acidic medium as shown in Scheme 37. Compounds were evaluated for in vitro cytotoxic activity against HepG2 and HL-7702 cancer cell lines, using MTT assay, considering SOR as standard reference compound.…”

Section: Triazole Fused With Phthalazinementioning

confidence: 99%

See 1 more Smart Citation

Synthetic and Medicinal Perspective of 1,2,4‐Triazole as Anticancer Agents

Rathod

Kumar

2022

Chemistry & Biodiversity

View full text Add to dashboard Cite

Cancer is still one of the leading causes of death worldwide. Many researchers are working to design and develop heterocyclic-based drugs with the potential to treat cancer at various stages. There is always an unmet need to discover new anticancer drugs to treat different types of cancer. Based on literature reports, it was evident that hybrid 1,2,4-triazoles exhibit a wide spectrum of biological potential (particularly potent anticancer activity), as compared to the corresponding monocyclic compounds. In this review, we summarized fused/hybrid 1,2,4-triazole and poly-functionalized 1,2,4-triazoles as anticancer agents. Triazole may be fused with other heterocyclic scaffolds like pyrimidine, pyridine, piperidine, quinoxaline, quinazoline, thiadiazine, indole, phthalazine etc. A clear explanation of the method of synthesis, structure-activity relationship, and in vitro results plus the inhibitory concentration of new molecules are focused on in this review article.

show abstract

Section: Synthesis and Biological Evaluation Of Isolated/functionaliz...mentioning

confidence: 95%

Section: Triazole Fused With Phthalazinementioning

confidence: 99%

Synthetic and Medicinal Perspective of 1,2,4‐Triazole as Anticancer Agents

Rathod

Kumar

2022

Chemistry & Biodiversity

View full text Add to dashboard Cite

show abstract

“…HDAC6 displays unique structure and cellular localization. It has a wider range of biological functions than other isoforms [ 6 , 7 ]. Unlike many other HDACs, HDAC6 shows cytoplasmic localization.…”

Section: Role Of Hdac6 In Cancer Cell Proliferationmentioning

confidence: 99%

“…Unlike other HDACs, the development of HDAC6-specific inhibitors has been relatively successful [ 6 , 7 , 47 ]. NN-390, the first HDAC6-selective inhibitor, has shown therapeutic potential for Group 3 medulloblastoma (MB), an aggressive pediatric brain tumor associated with leptomeningeal metastases and therapy resistance [ 48 ].…”

Section: Hdac6-selective Inhibitorsmentioning

confidence: 99%

Targeting HDAC6 to Overcome Autophagy-Promoted Anti-Cancer Drug Resistance

Shim

Jeoung

2022

IJMS

View full text Add to dashboard Cite

Histone deacetylases (HDACs) regulate gene expression through the epigenetic modification of chromatin structure. HDAC6, unlike many other HDACs, is present in the cytoplasm. Its deacetylates non-histone proteins and plays diverse roles in cancer cell initiation, proliferation, autophagy, and anti-cancer drug resistance. The development of HDAC6-specific inhibitors has been relatively successful. Mechanisms of HDAC6-promoted anti-cancer drug resistance, cancer cell proliferation, and autophagy are discussed. The relationship between autophagy and anti-cancer drug resistance is discussed. The effects of combination therapy, which includes HDAC6 inhibitors, on the sensitivity of cancer cells to chemotherapeutics and immune checkpoint blockade are presented. A summary of clinical trials involving HDAC6-specific inhibitors is also presented. This review presents HDAC6 as a valuable target for developing anti-cancer drugs.

show abstract

“…In leukemia cells, HDAC6 inhibitors can inhibit the process of α-tubulin deacetylation by HDAC6, disrupting the microtubule dynamics system and ultimately inhibiting cancer cell migration ( 12 ). Furthermore, HDAC6 inhibition can block the process of proliferation and invasion of gastric cancer cells ( 13 , 14 ). Thus, targeting HDAC6 could be a promising therapeutic option for gastric cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

Canagliflozin, characterized as a HDAC6 inhibitor, inhibits gastric cancer metastasis

Jiang

2022

Front. Oncol.

View full text Add to dashboard Cite

Gastric cancer is a common gastrointestinal cancer. Survival outcome for patients with the recurrence or metastasis remains poor due to the lack of effective targeting drugs. The mechanisms of non-histone acetylation modifications are key epigenetic regulations that participate in various biological processes. HDAC6 is mostly located in the cytoplasm to deacetylate non-histone substrates, which has been identified as a critical promoter of many oncogenic pathways in cancers, including gastric cancer. Nevertheless, its inhibitor has not been applied in gastric cancer clinically. In this study, we identified canagliflozin as an active HDAC6-targeted inhibitor from FDA-approved Drug Library by enzymatic assay. The strong affinity of the compounds with HDAC6 was further verified by surface plasmon resonance (SPR) and cellular thermal shift assay (CETSA). In addition, molecular docking showed that canagliflozin could bind to the active pocket of HDAC6 and form interactions with key residues. Further experiments revealed that canagliflozin could effectively inhibit the migration and epithelial-mesenchymal-transition (EMT) of gastric cancer cells in vitro and in vivo. These results reveal a novel finding that canagliflozin has the potential to be an effective agent in inhibiting gastric cancer metastasis.

show abstract

Identification of novel 1,3-diaryl-1,2,4-triazole-capped histone deacetylase 6 inhibitors with potential anti-gastric cancer activity

Cited by 19 publications

References 50 publications

Synthetic and Medicinal Perspective of 1,2,4‐Triazole as Anticancer Agents

Synthetic and Medicinal Perspective of 1,2,4‐Triazole as Anticancer Agents

Targeting HDAC6 to Overcome Autophagy-Promoted Anti-Cancer Drug Resistance

Canagliflozin, characterized as a HDAC6 inhibitor, inhibits gastric cancer metastasis

Contact Info

Product

Resources

About