Vitamin D3 is not a real vitamin D because it can be produced in the skin by sunlight irradiation of 7-dehydrocholesterol. It is now generally accepted that vitamin D3, before eliciting its biological activity, must be hydroxylated to 1,25-dihydroxyvitamin D3 (1,25D). This metabolite is considered the hormonally active form of vitamin D3 and interacts with the vitamin D nuclear receptor (VDR) to control important biological functions such as mineral homeostasis, cell differentiation, cell-antiproliferation, cell grow, apoptosis and the immune system. The fact that VDR has been found in more than 30 target tissues and cell tumors has led to the consideration that 1,25D is involved in a wider array of biological functions including cancer prevention.
Over the past 30 years we have dedicated our efforts to the development of convergent synthetic routes that were used to synthesize the most important vitamin D3 metabolites and numerous vitamin D3 analogues functionalized in various parts of the parent vitamin D skeleton. The biological properties of these analogues have served to understand the structure of the bioactive vitamin D conformation. More recently, and on the basis of the crystal structure of 1,25D in complex with VDR, we have designed by docking calculations and synthesized a few vitamin D analogues with higher potency than the natural hormone.
Our interest in the field of vitamin D is now focused on the application of new and flexible synthetic routes to the total synthesis of 1,25D and new vitamin D3 analogues which are difficult to obtain by the current synthetic strategies. It is expected that the new analogues will serve to understand the mechanism of action of the natural hormone in particular the non-genomic rapid responses and for the isolation of other VDR, for example membrane-VDR. Particular points of interest are the development of new vitamin D analogues with selective properties and low or negligible calcemic effects for treatment of cancer (colon, breast, lung and prostate cancers), osteoporosis, psoriasis and vitamin D-resistant rickets. You are welcome to our circle site to see our recent work and our external collaborations in the areas of crystal structure and biological activity.