Dataset Information

Synthetic Studies toward the Natural Product Tripartin, the First Natural Histone Lysine Demethylase Inhibitor.

ABSTRACT: An efficient synthesis of dimethyl tripartin as a synthetic precursor of natural product tripartin, the first natural specific inhibitor of histone H3 lysine 9 demethylase KDM4, is described. The synthesis of dimethyl tripartin was achieved in a six-step longest linear sequence starting from commercially available 3,5-dimethoxy benzaldehyde with 21% overall yield, using ClTi(O ⁱ Pr)₃-mediated dichloromethine insertion as the key step.

SUBMITTER: Dethe DH

PROVIDER: S-EPMC6645238 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Synthetic Studies toward the Natural Product Tripartin, the First Natural Histone Lysine Demethylase Inhibitor.

Dethe Dattatraya H DH Boda Raghavender R

ACS omega 20180816 8

An efficient synthesis of dimethyl tripartin as a synthetic precursor of natural product tripartin, the first natural specific inhibitor of histone H3 lysine 9 demethylase KDM4, is described. The synthesis of dimethyl tripartin was achieved in a six-step longest linear sequence starting from commercially available 3,5-dimethoxy benzaldehyde with 21% overall yield, using ClTi(O i Pr)3-mediated dichloromethine insertion as the key step. ...[more]

PMID: 31459063

Similar Datasets

Project description:ObjectiveAberrant activity of androgen receptor (AR) is the primary cause underlying development and progression of prostate cancer (PCa) and castration-resistant PCa (CRPC). Androgen signaling regulates gene transcription and lipid metabolism, facilitating tumor growth and therapy resistance in early and advanced PCa. Although direct AR signaling inhibitors exist, AR expression and function can also be epigenetically regulated. Specifically, lysine (K)-specific demethylases (KDMs), which are often overexpressed in PCa and CRPC phenotypes, regulate the AR transcriptional program.MethodsWe investigated LSD1/UTX inhibition, two KDMs, in PCa and CRPC using a multi-omics approach. We first performed a mitochondrial stress test to evaluate respiratory capacity after treatment with MC3324, a dual KDM-inhibitor, and then carried out lipidomic, proteomic, and metabolic analyses. We also investigated mechanical cellular properties with acoustic force spectroscopy.ResultsMC3324 induced a global increase in H3K4me2 and H3K27me3 accompanied by significant growth arrest and apoptosis in androgen-responsive and -unresponsive PCa systems. LSD1/UTX inhibition downregulated AR at both transcriptional and non-transcriptional level, showing cancer selectivity, indicating its potential use in resistance to androgen deprivation therapy. Since MC3324 impaired metabolic activity, by modifying the protein and lipid content in PCa and CRPC cell lines. Epigenetic inhibition of LSD1/UTX disrupted mitochondrial ATP production and mediated lipid plasticity, which affected the phosphocholine class, an important structural element for the cell membrane in PCa and CRPC associated with changes in physical and mechanical properties of cancer cells.ConclusionsOur data suggest a network in which epigenetics, hormone signaling, metabolite availability, lipid content, and mechano-metabolic process are closely related. This network may be able to identify additional hotspots for pharmacological intervention and underscores the key role of KDM-mediated epigenetic modulation in PCa and CRPC.

Dataset Information

Synthetic Studies toward the Natural Product Tripartin, the First Natural Histone Lysine Demethylase Inhibitor.

Publications

Synthetic Studies toward the Natural Product Tripartin, the First Natural Histone Lysine Demethylase Inhibitor.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets