1009815-87-5Relevant articles and documents
Largazole arrests cell cycle at g1 phase and triggers proteasomal degradation of E2F1 in lung cancer cells
Wu, Li-Chuan,Wen, Zhe-Sheng,Qiu, Ya-Tao,Chen, Xiao-Qin,Chen, Hao-Bin,Wei, Ming-Ming,Liu, Zi,Jiang, Sheng,Zhou, Guang-Biao
, p. 921 - 926 (2013)
Aberration in cell cycle has been shown to be a common occurrence in lung cancer, and cell cycle inhibitor represents an effective therapeutic strategy. In this study, we test the effects of a natural macrocyclic depsipeptide largazole on lung cancer cells and report that this compound potently inhibits the proliferation and clonogenic activity of lung cancer cells but not normal bronchial epithelial cells. Largazole arrests cell cycle at G1 phase with up-regulation of the expression of cyclin-dependent kinase inhibitor p21. Interestingly, largazole enhances the E2F1-HDAC1 binding affinity and induces a proteasomal degradation of E2F1, leading to suppression of E2F1 function in lung cancer but not normal bronchial epithelial cells. Because E2F1 is overexpressed in lung cancer tumor samples, these data indicate that largazole is an E2F1-targeting cell cycle inhibitor, which bears therapeutic potentials for this malignant neoplasm.
Concise total synthesis of largazole
Xiao, Qiong,Wang, Li-Ping,Jiao, Xiao-Zhen,Liu, Xiao-Yu,Wu, Qian,Xie, Ping
, p. 940 - 949 (2010)
The concise total synthesis of largazole was accomplished. The key step included the use of the Nagao thiazolidinethione auxiliary for the diastereoselective acetate aldol reaction and it acts as an acylating agent for the peptide formation.
Synthesis and biological activity of largazole and derivatives
Seiser, Tobias,Kamena, Faustin,Cramer, Nicolai
, p. 6483 - 6485 (2008)
A modular synthesis of the marine natural product largazole and related synthetic analogues is described. Largazole was prepared in 19% overall yield through a synthetic route with a longest linear sequence of nine steps. Activity tests showed the necessity of the thiobutenyl moiety for antiproliferative activity. (Chemical Equation Presented).
Total syntheses of the histone deacetylase inhibitors largazole and 2-epi-largazole: Application of N-Heterocyclic carbene mediated acylations in complex molecule synthesis
Wang, Bo,Huang, Po-Hsien,Chen, Ching-Shih,Forsyth, Craig J.
, p. 1140 - 1150 (2011)
Details of the evolution of strategies toward convergent assembly of the histone deacetylase inhibiting natural product largazole exploiting γ,δ-unsaturated-α,β-epoxy-aldehydes and a thiazole-thiazoline containing ω-amino-acid are described. The initial N-heterocyclic carbene mediated redox amidation exploying these two types of building blocks representing largazole's structural domains of distinct biosynthetic origin directly afforded the seco-acid of largazole. This was accomplished without any protecting groups resident upon either thioester bearing epoxy-aldehyde or the tetrapeptide. However, the ineffective production of largazole via the final macrolactonization led to an alternative intramolecular esterification/macrolactamization strategy employing the established two building blocks. This provided largazole along with its C2-epimer via an unexpected inversion of the α-stereocenter at the valine residue. The biological evaluation demonstrated that both largazole and 2-epi-largazole led to dose-dependent increases of acetylation of histone H3, indicating their potencies as class I histone deacetylase selective inhibitiors. Enhanced p21 expression was also induced by largazole and its C2 epimer. In addition, 2-epi-largazole displayed more potent activity than largazole in cell viability assays against PC-3 and LNCaP prostate cancer cell lines.
PROCESS FOR THE PREPARATION OF CYCLIC DEPSIPEPTIDES
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, (2015/12/17)
Processes for preparing compounds of Formula (1) and Formula (2) are described, wherein X, Y, Z, R1-R7, L and n are defined herein. Intermediates useful in the preparation of the compounds of Formula (1) and Formula (2) are also described.
