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D Derivatives (d + derivative)
Selected AbstractsCooperative antitumor effects of vitamin D3 derivatives and rosemary preparations in a mouse model of myeloid leukemiaINTERNATIONAL JOURNAL OF CANCER, Issue 12 2006Hagar Sharabani Abstract 1,,25-dihydroxyvitamin D3 (1,25D3) is a powerful differentiation agent, which has potential for treatment of myeloid leukemias and other types of cancer, but the calcemia produced by pharmacologically active doses precludes the use of this agent in the clinic. We have shown that carnosic acid, the major rosemary polyphenol, enhances the differentiating and antiproliferative effects of low concentrations of 1,25D3 in human myeloid leukemia cell lines (HL60, U937). Here we translated these findings to in vivo conditions using a syngeneic mouse leukemia tumor model. To this end, we first demonstrated that as in HL60 cells, differentiation of WEHI-3B D, murine myelomonocytic leukemia cells induced by 1 nM 1,25D3 or its low-calcemic analog, 1,25-dihydroxy-16-ene-5,6-trans-cholecalciferol (Ro25-4020), can be synergistically potentiated by carnosic acid (10 ,M) or the carnosic acid-rich ethanolic extract of rosemary leaves. This effect was accompanied by cell cycle arrest in G0+G1 phase and a marked inhibition of cell growth. In the in vivo studies, i.p. injections of 2 ,g Ro25-4020 in Balb/c mice bearing WEHI-3B D, tumors produced a significant delay in tumor appearance and reduction in tumor size, without significant toxicity. Another analog, 1,25-dihydroxy-16,23Z-diene-20-epi-26,27-hexafluoro-19-nor-cholecalciferol (Ro26-3884) administered at the same dose was less effective than Ro25-4020 and profoundly toxic. Importantly, combined treatment with 1% dry rosemary extract (mixed with food) and 1 ,g Ro25-4020 resulted in a strong cooperative antitumor effect, without inducing hypercalcemia. These results indicate for the first time that a plant polyphenolic preparation and a vitamin D derivative can cooperate not only in inducing leukemia cell differentiation in vitro, but also in the antileukemic activity in vivo. These data may suggest novel protocols for chemoprevention or differentiation therapy of myeloid leukemia. © 2006 Wiley-Liss, Inc. [source] Management of secondary hyperparathyroidism of dialysis patientsNEPHROLOGY, Issue 2003Tadao AKIZAWA SUMMARY: Hyperphosphatemia, vitamin D deficiency, and resulted hypocalcemia have been regarded as classical pathogeneses of secondary hyperparathyroidism. These factors have been treated by the administration of phosphorus binder and vitamin D derivatives. However, these therapies have not brought about a successful result for the prevention and treatment of secondary hyperparathyroidism. The reason could be mainly attributed to the hypercalcemia that results from the administration of calcium salts as a phosphorus binder and the calcemic action of vitamin D. To prevent hypercalcemia, non-calcium containing phosphorus binder (sevelamer hydrochloride) and vitamin D analogues, which suppress PTH secretion with minimum calcemic action, have been developed. These new vitamin D analogues include 19-nor-1-alpha, 25-dihydroxyvitamin D2 (paricalcitol), 1-alpha-hydroxyvitamin D2 (doxercalciferol), 22oxa-calcitriol (maxacalcitol) and F6-calcitriol (falecalcitriol). Furthermore, calcimimetics that stimulate calcium-sensing receptor of parathyroid cells as calcium and suppress PTH secretion are now under clinical trial. Percutaneous direct injection therapy of vitamin D, vitamin D analogue or calcimimetics into parathyroid gland has also been reported. The combination of these new strategies is expected to effectively and safely suppresses secondary hyperparathyroidism that has been resistant to conventional medical treatments. [source] Bis(enaminones): Key intermediates for novel ,,,-bis(pyrazolylphenoxy), bis(pyranylphenoxy), and bis(benzo[b]furanylphenoxy) alkanesJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 2 2009Ashraf A. Abbas New bis(enaminone) derivatives, 5a,b and 9a,b, were prepared in good yields. Their synthetic utilities as key intermediates for the synthesis of novel bis(pyrazole) 12a,b, bis(pyrane) 17a,b, and bis(benzo[b]furan) 20a,d derivatives were also investigated. J. Heterocyclic Chem., 46, 340 (2009). [source] Asymmetric biomimetic oxidations of phenols using oxazolidines as chiral auxiliaries: the enantioselective synthesis of (+)- and (,)-dehydrodiconiferyl alcohol,JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 8-9 2006Maurizio Bruschi Abstract Stereoselective bimolecular radical coupling reactions of phenylpropenoid phenols are described. Evans's 2-oxazolidinone 11a,d derivatives of ferulic acid were prepared and oxidized to give dimeric benzofuran neolignan structures 12,13a,d in 40,50% overall yields. The chiral phenols were dimerized either enzymatically with hydrogen peroxide and horseradish peroxidase (HRP) or with silver oxide. The enantioselectivity after reductive cleavage of the chiral auxiliaries to give dehydrodiconiferyl alcohol ranged from 18% to 62% enantiomeric excess. The conformational analysis and the activation energy using semiempirical PM3 calculations on the intermediate quinomethides is used to explain the observed stereoselectivity. Copyright © 2006 John Wiley & Sons, Ltd. [source] Synthesis and Anti-Inflammatory Activity of Novel (4-Hydroxyphenyl)(2,4-dimethoxyphenyl) Methanone DerivativesARCHIV DER PHARMAZIE, Issue 8 2009Kambappa Vinaya Abstract In the scope of the research program aiming to perform the synthesis and pharmacological evaluation of novel possible anti-inflammatory compounds, in this manuscript, we report the synthesis of novel carboxamide 9a - d and thioamide 10a - d derivatives from the benzophenone and piperidine nucleus. Variation in the functional group at the N -terminal of piperidine led to two sets of compounds, bearing the carboxamide and thioamide, respectively. The characterization of this new class of compounds was performed with 1H-NMR, LC-MS, IR, and elemental analysis. The newly synthesized compounds were screened for their anti-inflammatory activity by carrageenan-induced foot pad oedema assay and were compared with a standard drug. All the compounds exhibited anti-inflammatory activity at the dose of 30 mg/kg p.o. with varying degree from 52 to 67% inhibition of oedema. The compounds 9d and 10d with dichloro and fluoro substitution showed more potent activity at 30 mg/kg p.o. than the standard drug. [source] | |||||||||||||