A novel small molecule hybrid of vorinostat and DACA displays anticancer activity against human hormone-refractory metastatic prostate cancer through dual inhibition of histone deacetylase and topoisomerase I

Yu, Chi; Pan, Shiow Lin; Chao, Shi Wei; Liu, Shih‐Ping; Hsu, Jui Ling; Yang, Yu; Li, Tsia Kun; Huang, Wei; Guh, Jih‐Hwa

doi:10.1016/j.bcp.2014.06.001

Cited by 27 publications

(15 citation statements)

References 49 publications

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“…0.04, SKW3/Clo without melatonin treatment vs. SKW3/Clo with melatonin treatment. [23]. Vorinostat treatment also significantly increased the cytotoxicity of clofarabine in NALM6/Clo cells and SKW3/Clo cells (Fig.…”

Section: Decreased Acetylation In Clofarabine-resistant Cells As Commentioning

confidence: 88%

Melatonin overcomes resistance to clofarabine in two leukemic cell lines by increased expression of deoxycytidine kinase

Yamanishi

Narazaki

Asano

2015

Experimental Hematology

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Section: Decreased Acetylation In Clofarabine-resistant Cells As Commentioning

confidence: 88%

Melatonin overcomes resistance to clofarabine in two leukemic cell lines by increased expression of deoxycytidine kinase

Yamanishi

Narazaki

Asano

2015

Experimental Hematology

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“…WJ35435 (6, Fig. 3), hybrid between SAHA and an acridine derivative known as a dual topo I/II inhibitor (DACA), is described as a potent HDAC inhibitor with preferential inhibition of HDAC1 and HDAC6 and selective inhibition of topo I [24]. Preclinical studies show antitumour activity against a model of human prostate carcinoma PC3, but the available data on biological evaluation does not allow a definitive conclusion on the therapeutic interest of the hybrid compound.…”

Section: Hybrid Compounds Incorporating Cytotoxic Moieties and Hdac Imentioning

confidence: 98%

Perspectives in the development of hybrid bifunctional antitumour agents

Musso

Dallavalle

Zunino

2015

Biochemical Pharmacology

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In spite of the development of a large number of novel target-specific antitumour agents, the single-agent therapy is in general not able to provide an effective durable control of the malignant process. The limited efficacy of the available agents (both conventional cytotoxic and novel target-specific) reflects not only the expression of defence mechanisms, but also the complexity of tumour cell alterations and the redundancy of survival pathways, thus resulting in tumour cell ability to survive under stress conditions. A well-established strategy to improve the efficacy of antitumour therapy is the rational design of drug combinations aimed at achieving synergistic effects and overcoming drug resistance. An alternative strategy could be the use of agents designed to inhibit simultaneously multiple cellular targets relevant to tumour growth/survival. Among these novel agents are hybrid bifunctional drugs, i.e. compounds resulting by conjugation of different drugs or containing the pharmocophores of different drugs. This strategy has been pursued using various conventional or target-specific agents (with DNA damaging agents and histone deacetylase inhibitors as the most exploited compounds). A critical overview of the most representative compounds is provided with emphasis on the HDAC inhibitor-based hybrid agents. In spite of some promising results, the actual pharmacological advantages of the hybrid agents remain to be defined. This commentary summarizes the recent advances in this field and highlights the pharmacological basis for a rational design of hybrid bifunctional agents.

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“…Further studies describing the effect of this potent hybrid 78 on resistant cell lines compared to the parent's combination are required. In 2014, Yu et al . developed hybrid (WJ35435) 80 as a new small molecule hybrid of SAHA and DACA N ‐[2‐(dimethylamino)ethyl]acridine‐4‐carboxamide ( 70 ), which is a topoisomerase1/2 inhibitor (Figure ).…”

Section: Design Of Dual Topoisomerase/hdac Inhibitorsmentioning

confidence: 99%

Chimeric HDAC inhibitors: Comprehensive review on the HDAC‐based strategies developed to combat cancer

Hesham

Lasheen

Abouzid

2018

Medicinal Research Reviews

120

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Recently, molecular hybridization paradigm became an interesting and smart way to defeat the multifaceted cancer disease by a single molecular entity that acts via several mechanisms just like a magic bullet. Also, HDAC is an important epigenetic target in drug discovery, and the HDAC inhibitors showed successful pattern as cytotoxic agents. Because of their flexible structure activity relationship, it was easy to link them to other anticancer scaffolds. So, many dual action HDAC inhibitors have been developed and most of these hybrids have higher potency than the constituting parents in fighting of the cancer cells. This review describes potential applications of chimeric HDAC inhibitors, which simultaneously modulate not only HDAC but also multiple targets, in treatment of relapsing and drug-resistant cancers. We have nearly collected most of the reported dual action HDAC inhibitors yet to provide a comprehensive guide for the drug discovery process for developing more efficient anticancer agents.

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A novel small molecule hybrid of vorinostat and DACA displays anticancer activity against human hormone-refractory metastatic prostate cancer through dual inhibition of histone deacetylase and topoisomerase I

Cited by 27 publications

References 49 publications

Melatonin overcomes resistance to clofarabine in two leukemic cell lines by increased expression of deoxycytidine kinase

Melatonin overcomes resistance to clofarabine in two leukemic cell lines by increased expression of deoxycytidine kinase

Perspectives in the development of hybrid bifunctional antitumour agents

Chimeric HDAC inhibitors: Comprehensive review on the HDAC‐based strategies developed to combat cancer

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