The influence of methyl groups at C-22 on their biological activity was examined. It was established that both in vitro and in vivo activity is strongly Small molecule library cell line dependent on the configuration of the stereogenic centers at C-20 and C-22. Introduction of the second methyl group at C-22 (analogues 5 and 6) generates the compounds that are slightly more potent than 1 alpha,25-(OH)(2)D-3
in the in vitro tests but much less potent in vivo. The greatest in vitro and in vivo biological activity was achieved when the C-20 is in the S configuration and the C-22 is in the R configuration. The building blocks for the synthesis, the respective (20R,22R)-, (20R,22S)-, (20S,22R)-, and (20S,22S)-diols, were obtained by fractional crystallization of mixtures of the corresponding diastereomers. Structures and absolute configurations of the diols 21a, 21b, and 22a as well as analogues 3a, 5, and 6 were confirmed by the X-ray crystallography.”
“To develop formulations of carnosic acid nanoparticles and to assess their in WH-4-023 nmr vivo efficacy to enhance the expression of neurotrophins in rat model. Carnosic acid loaded chitosan nanoparticles were
prepared by ionotropic gelation technique using central composite design. Response surface methodology was used to assess the effect of three factors namely chitosan concentration (0.1-1% w/v), tri-poly phosphate concentration (0.1-1% w/v) and sonication time (2-10 min) on the response variables such as particle size, zeta potential, drug encapsulation efficiency and drug release. The neurotrophins level in the rat brain upon intranasal administration Selleckchem HSP990 of optimized batch of carnosic acid nanoparticles was determined. The experimental values for the formulation were in good agreement with those predicted by the mathematical
models. A single intranasal administration of the optimized formulation of carnosic acid nanoparticles was sufficient to result in comparable levels of endogenous neurotrophins level in the brain that was almost on par with four, once a day intranasal administration of solution in rats. The results clearly demonstrated the fact that nanoparticulate drug delivery system for intranasal administration of carnosic acid would require less number of administrations to elicit the required pharmacological activity owing to its ability to localize on the olfactory mucosal region and provide controlled delivery of carnosic acid for prolonged time periods.”
“Cutaneous melanoma is one of the leading causes of cancer-related death. Malignant transformation of epidermal melanocytes is a multifactorial process involving cell cycle and death control pathways. The purpose of this study was to analyze the immunohistochemical expression of cell-cycle-related and apoptosis-related proteins in cutaneous superficial spreading melanomas using the tissue microarray technique to further understand tumor development A total of 20 samples of in-situ melanomas and 44 melanomas <= 1.