The biologically active metabolite of vitamin D - calcitriol - is a hormone involved in the regulation of calcium-phosphate homeostasis, immunological processes and cell differentiation, being therefore essential for the proper functioning of the human body. This suggests many applications of this steroid in the treatment of diseases such as rickets, psoriasis and some cancers. Unfortunately, using therapeutic doses of calcitriol is associated with high concentrations of this compound which causes hypercalcemia.
View Article and Find Full Text PDFWe are commenting recent discoveries on the presence of L-DOPA, dopamine, 5-hydroxytryptophan, tryptamine, serotonin, -acetylserotonin, melatonin, 2-hydroxymelatonin, AFMK and AMK in honey. Serotonin and melatonin, products of the tryptophan metabolism, are widely produced in nature, serving as hormones, neurotransmitters, biological regulators, neurotransmitters and antioxidants, in a context dependent fashion. Dopamine and tryptamine are important neurotransmitters across different species.
View Article and Find Full Text PDFNew and more efficient routes of chemical synthesis of vitamin D (D) hydroxy (OH) metabolites, including 20S(OH)D, 20S,23S(OH)D and 20S,25(OH)D, that are endogenously produced in the human body by CYP11A1, and of 20S,23R(OH)D were established. The biological evaluation showed that these compounds exhibited similar properties to each other regarding inhibition of cell proliferation and induction of cell differentiation but with subtle and quantitative differences. They showed both overlapping and differential effects on T-cell immune activity.
View Article and Find Full Text PDFA new series of highly biologically active (20S,22R)-1α,25-dihydroxy-22-methyl-2-methylene-vitamin D analogs, possessing different side chains, have been efficiently prepared as potential agents for medical therapy. Design of these synthetic targets was based on the analysis of the literature data and molecular docking experiments. The synthetic strategy involved Sonogashira coupling of the known A-ring dienyne with the C,D-ring enol triflates, obtained from the corresponding Grundmann ketones.
View Article and Find Full Text PDFContinuing our studies aimed at A-ring modified vitamin D compounds, we designed novel 19-norcalcitriol derivatives bearing at C-2 pegylated chains of different lengths. The terminal fragments of these substituents contain hydroxyls or moieties possessing nitrogen and/or sulfur atoms capable of transition metal ions complexation. Also, two conjugate-type platinum(II) complexes of 19-norcalcitriol were obtained in which l-methionine served as chelating moiety.
View Article and Find Full Text PDF20()-Hydroxyvitamin D3 (20(OH)D3) is an endogenous metabolite produced by the action of CYP11A1 on the side chain of vitamin D3 (D3). 20(OH)D3 can be further hydroxylated by CYP11A1, CYP27A1, CYP24A1 and/or CYP27B1 to several hydroxyderivatives. CYP11A1 also hydroxylates D3 to 22-monohydroxyvitamin D3 (22(OH)D3), which is detectable in the epidermis.
View Article and Find Full Text PDFHormonally active vitamin D metabolite, calcitriol, plays an important role in calcium-phosphate homeostasis, immune system actions and cell differentiation. Although anticancer activity of calcitriol is well documented and thousands of its analogs have been synthesized, none has been approved as a potential drug against cancer. Therefore, we attempted to introduce the cytotoxic effect to the calcitriol molecule by its linking to cisplatin.
View Article and Find Full Text PDFJ Steroid Biochem Mol Biol
January 2019
The results presented in this paper constitute an extension of our synthetic efforts focused on 19-norvitamin D compounds possessing elongated 2-alkylidene substituents. Based on our previous results, molecular modeling studies, and docking experiments, we selected a novel 19-norcalcitriol analog with long chain at C-2 containing several ether moieties and terminated by 2-(pyridin-2'-yl)ethylamino fragment. It was expected that such structural modification might allow binding of transition metal by the ligand, increase solubility of the formed complexes as well as improve their affinity to the VDR.
View Article and Find Full Text PDFContinuing our structure-activity studies on the vitamin D analogs with the altered intercyclic seco-B-ring fragment, we designed compounds possessing dienyne system conjugated with the benzene D ring. Analysis of the literature data and the docking experiments seemed to indicate that the target compounds could mimic the ligands with a good affinity to the vitamin D receptor (VDR). Multi-step synthesis of the C/D-ring building block of the tetralone structure was achieved and its enol triflate was coupled with the known A-ring fragments, possessing conjugated enyne moiety, using Sonogashira protocol.
View Article and Find Full Text PDFJ Steroid Biochem Mol Biol
March 2018
Pronounced biological potency of 19-norvitamin D compounds as well as interesting biological action of the vitamin D analogs possessing elongated side chains encouraged us to expand the scope of our structure-activity studies to encompass such modifications of the 1α,25-(OH)D (calcitriol) molecule. The aim of our studies was the synthesis of calcitriol analog, designed on the basis of results of molecular modeling and docking experiments, and characterized by a presence of a long, nitrogen-containing substituent attached to carbon 26, and an exomethylene moiety transferred from C-10 to C-2. The convergent synthesis of such 19-norcalcitriol compound, described in this communication, consisted of the preparation and combining four building blocks.
View Article and Find Full Text PDFOn the basis of the literature data, our previous research work and docking experiments, we designed novel 19-norvitamin D compounds having elongated 2-alkylidene substituents. These 19-norcalcitriol derivatives have attached 2-(3'-aminopropylidene) substituent in which the nitrogen atom bears acyl residue derived from succinic acid and l-methionine. Both compounds were obtained by the same synthetic strategy involving Julia coupling of the A-ring ketone with the known C/D-ring sulfone.
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