Exploring alternative Zn-binding groups in the design of HDAC inhibitors: Squaric acid, N-hydroxyurea, and oxazoline analogues of SAHA

Hanessian, Stephen; Vinci, Valerio; Auzzas, Luciana; Marzi, Mauro; Giannini, Giuseppe

doi:10.1016/j.bmcl.2006.06.090

Cited by 27 publications

(25 citation statements)

References 31 publications

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“…Attempted replacement of the hydroxamate group by the other functional groups such as alcohol, carboxylic acid, and amide, failed to provide any significant HDAC inhibitory activity (Compound 8 , 9 , and 10 ). This is not surprising in light of other publications 16,17…”

supporting

confidence: 58%

Isoxazole moiety in the linker region of HDAC inhibitors adjacent to the Zn-chelating group: Effects on HDAC biology and antiproliferative activity

Tapadar

Luchini

et al. 2009

Bioorganic & Medicinal Chemistry Letters

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supporting

confidence: 58%

Isoxazole moiety in the linker region of HDAC inhibitors adjacent to the Zn-chelating group: Effects on HDAC biology and antiproliferative activity

Tapadar

Luchini

et al. 2009

Bioorganic & Medicinal Chemistry Letters

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“…HU can be a satisfactory hydroxamate replacement if the rest of the molecule can compensate for the unfavorable desolvation effect on the binding affinity of hydrophilic HU [30]. This might be the case of lipophilic BOU (XlogP = 5.1) and MHCU (XlogP = 3.4) [32]. Higher lipophilic character of BOU may also account for its increased cellular uptake and thus more pronounced in vitro effects compared to MHCU.…”

Section: Resultsmentioning

confidence: 99%

Antitumor Mechanisms of Amino Acid Hydroxyurea Derivatives in the Metastatic Colon Cancer Model

Šaban

Stepanić

Srđan

et al. 2013

IJMS

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The paper presents a detailed study of the biological effects of two amino acid hydroxyurea derivatives that showed selective antiproliferative effects in vitro on the growth of human tumor cell line SW620. Tested compounds induced cell cycle perturbations and apoptosis. Proteins were identified by proteomics analyses using two-dimensional gel electrophoresis coupled to mass spectrometry, which provided a complete insight into the most probable mechanism of action on the protein level. Molecular targets for tested compounds were analyzed by cheminformatics tools. Zinc-dependent histone deacetylases were identified as potential targets responsible for the observed antiproliferative effect.

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“…Numerous HDIs were designed using this technique [178][179][180][181]. In addition, this approach provides insight into patentability of lead candidates.…”

Section: Bioisosteric Morphingmentioning

confidence: 99%

Histone Deacetylase Inhibitors in Cancer Therapy: Latest Developments, Trends and Medicinal Chemistry Perspective

Balakin¹,

Ivanenkov²,

Kiselyov³

et al. 2007

ACAMC

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Regulation of gene expression is mediated by several mechanisms such as DNA methylation, ATP-dependent chromatin remodeling, and post-translational modifications of histones. The latter mechanism includes dynamic acetylation and deacetylation of epsilon-amino groups of lysine residues present in the tail of the core histones. Enzymes responsible for the reversible acetylation/deacetylation processes are histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively. There are three mammalian HDAC families, namely HDACs I, II and III based on their sequence homology. Inhibitors of HDACs induce hyperacetylation of histones that modulate chromatin structure and gene expression resulting in growth arrest, cell differentiation, and apoptosis of tumor cells. In addition, HDAC inhibitors enhance efficacy of anticancer agents that target DNA. Several formidable challenges associated with their development include non-specific toxicity and poor PK properties, including cell permeability. In this review, we comment on the current progress in design, discovery, in vitro/ex vivo activity and clinical potential of the synthetic modulators of HDACs.

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Exploring alternative Zn-binding groups in the design of HDAC inhibitors: Squaric acid, N-hydroxyurea, and oxazoline analogues of SAHA

Cited by 27 publications

References 31 publications

Isoxazole moiety in the linker region of HDAC inhibitors adjacent to the Zn-chelating group: Effects on HDAC biology and antiproliferative activity

Isoxazole moiety in the linker region of HDAC inhibitors adjacent to the Zn-chelating group: Effects on HDAC biology and antiproliferative activity

Antitumor Mechanisms of Amino Acid Hydroxyurea Derivatives in the Metastatic Colon Cancer Model

Histone Deacetylase Inhibitors in Cancer Therapy: Latest Developments, Trends and Medicinal Chemistry Perspective

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