Design and synthesis of functionalized piperazin-1yl-(E)-stilbenes as inhibitors of 17α-hydroxylase-C17,20-lyase (Cyp17)

The synthesis of steroid hormones is critical to human physiology and improper regulation of either the synthesis of these key molecules or activation of the associated receptors can lead to disease states. This has led to intense interest in developing compounds capable of modulating the synthesis of steroid hormones. Compounds capable of inhibiting Cyp19 (Aromatase), a key enzyme in the synthesis of estrogens, have been successfully employed as breast cancer therapies, while inhibitors of Cyp17 (17α-hydroxylase-17,20-lyase), a key enzyme in the synthesis of glucocorticoids, mineralocorticoids and steroidal sex hormones, are a key component of prostate cancer therapy. Inhibition of CYP17 has also been suggested as a possible target for the treatment of Cushing Syndrome and Metabolic Syndrome. We have identified two novel series of stilbene based CYP17 inhibitors and demonstrated that exemplary compounds in these series have pharmacokinetic properties consistent with orally delivered drugs. These findings suggest that compounds in these classes may be useful for the treatment of diseases and conditions associated with improper regulation of glucocorticoids synthesis and glucocorticoids receptor activation.     

Effect of High Temperature on Photosynthetic Electron Transport Activities of the Cyanobacterium Spirulina Platensis

The activities of photosystem 2 (PS2) and whole chain electron transport declined in high temperature treated cells at the room temperature beyond 35 °C, while photosystem 1 (PS1) showed increased activity. Thylakoid membrane studies did not exhibit increase in PS1 activity indicating that the enhancement of PS1 activity is due to permeability change of cell membranes. However, the electron transport activity measured from reduced duroquinone to methylviologen which involves intersystem electron transport was extremely sensitive to high temperature. The activity of PS2 at different irradiance, which was accompanied by alterations in absorption and fluorescence emission properties, indicated changes in the energy transfer processes within phycobilisomes. Thus high temperature has multiple target sites in photosynthetic electron transport system of Spirulina platensis.