Design, synthesis, and biological evaluation of novel androst-17β-amide structurally related compounds as dual 5α-reductase inhibitors and androgen receptor antagonists.

Prostate cancer (PCa) is the second leading cause of death in men. Apart from androgen receptor, 5α-reductase has also been recognized as a potential target. In this study, a series of androst-17β-amide compounds have been designed and synthesized targeting both AR and 5α-reductase.

Discovery of Small-Molecule Antagonists of the H3K9me3 Binding to UHRF1 Tandem Tudor Domain.

Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is a multidomain protein that plays a critical role in maintaining DNA methylation patterns through concurrent recognition of hemimethylated DNA and histone marks by various domains, and recruitment of DNA methyltransferase 1 (DNMT1). UHRF1 is overexpressed in various cancers, including breast cancer. The tandem tudor domain (TTD) of UHRF1 specifically and tightly binds to histone H3 di- or trimethylated at lysine 9 (H3K9me2 or H3K9me3, respectively), and this binding is essential for UHRF1 function.

Generation of trans-arachidonic acid under nitrative stress is associated with upregulation of thromponsdin-1 in diabetic rats.

Background: Trans-arachidonic acids (TAAs), newly discovered markers of nitrative stress and the major products of nitrogen dioxide (NO2(·))-mediated isomerization of arachidonic acid (AA), represent a new mechanism of NO2(·)-induced toxicity. It has been reported that TAAs were generated in oxygen-induced microvascular degeneration model and TAAs were also generated in a diabetic retinopathy (DR) model. In this study, we examined high glucose-induced nitrative stress damage and TAAs levels and explored the possible mechanisms for DR caused by reactive nitrogen species.

Tuning the acyclic ether moiety of anticancer agent AA005 with conformationally constrained fragments.

A new series of anticancer annonaceous acetogenin mimetics were designed, synthesized, and evaluated based on our previously developed compound AA005, in which a variety of conformationally constrained fragments were introduced. Parallel syntheses of all new compounds were accomplished by replacement of the acyclic bis-ether functionality of AA005 with certain conformationally constrained fragments. Slight effects to the anticancer activity were exerted by altering stereochemistries in the middle modification region.

Effects of generated trans-arachidonic acids on retinal capillary during nitrative stress in diabetic rats.

Purpose: To investigate whether the trans-arachidonic acids (TAAs) change in diabetic conditions and the effect on capillary cells and its possible mechanism.

Methods: Diabetes was induced by intraperitoneal injection of streptozotocin at 60 mg kg(-1) body weight. The amount of TAAs and arachidonic acid (AA) in serum of diabetic rats was measured by the gas chromatography and mass spectrometry method and the ratio of the peak area of TAAs to AA with a selected ion of 79 was estimated by group t test.