Impairment of prostate cancer cell growth by a selective and reversible lysine-specific demethylase 1 inhibitor.

Post-translational modifications of histones by chromatin modifying enzymes regulate chromatin structure and gene expression. As deregulation of histone modifications contributes to cancer progression, inhibition of chromatin modifying enzymes such as histone demethylases is an attractive therapeutic strategy to impair cancer growth. Lysine-specific demethylase 1 (LSD1) removes mono- and dimethyl marks from lysine 4 or 9 of histone H3.

Principles, implementation, and application of biology-oriented synthesis (BIOS).

Biology-oriented synthesis (BIOS) represents an alternative approach for the generation of compound collections for biological applications. In BIOS, biologically relevant and prevalidated scaffold structures, such as core structures of natural products or known drugs, are employed as scaffolds for the generation of compound collections with focused diversity. In this review, we discuss the underlying concept of the BIOS approach, and its practical implementation in library design and synthesis.

Biology-oriented combined solid- and solution-phase synthesis of a macroline-like compound collection.

Macrolines constitute a class of natural products that has more than 100 members and displays diverse biological activities. These compounds feature a cycloocta[b]indole scaffold that represents an interesting target structure for biology-oriented synthesis (BIOS). We have presented a solid-phase synthesis of isomerically pure cycloocta[b]indoles by employing the Pictet-Spengler reaction and the Dieckmann cyclization as key steps.

Gamma-pyrone natural products--a privileged compound class provided by nature.

In "Biology Oriented Synthesis" (BIOS), the inherent biological relevance of natural products is employed for the design and synthesis of compound libraries. Towards this end, library generation in BIOS is focused on compound classes from biologically relevant space such as the natural product space or also the drug space and only scaffolds of these areas of proven relevance are employed for synthesis of small focused libraries with limited diversity. We here present a short overview of gamma-pyrone natural products, highlighting their biological properties and their potential applicability in a BIOS of a compound library.

Synthesis and unexpected reactivity of Si-H functionalized dithieno[3,2-b:2',3'-d]phospholes.

[reaction: see text]. Si-H functionalized, blue light-emitting dithieno[3,2-b:2',3'-d]phospholes are accessible by reaction of an appropriate bithiophene precursor with a dichlorophosphane. Subsequent functionalization of the central phosphorus center allows for a fine-tuning of the optoelectronic properties of the material.