15981-86-9Relevant academic research and scientific papers
Mitochondrial mode of action of a thymidine-based cisplatin analogue breaks resistance in cancer cells
Onambele, Liliane A.,Koth, Daniel,Czaplewska, Justyna A.,Schubert, Ulrich S.,Goerls, Helmar,Yano, Shigenobu,Obata, Makoto,Gottschaldt, Michael,Prokop, Aram
, p. 14498 - 14505 (2010)
Cisplatin analogue complexes with platinum(II) and palladium(II) starting from 3′,5′-diamino-3′,5′-dideoxy-thymidines were synthesized, both with the D-erythro- and D-threo configurations. Complexes of the general formula [MCl2L] were obtained and characterized. NMR spectroscopic measurements and single crystal X-ray structure analysis showed that the metal centers are coordinated to the ligands by the amino groups in 3′- and 5′-positions and not through the thymine moiety. All ligands and complexes showed no significant in vitro activities except thymiplatin (cis-dichloro(3′,5′-diamino-3′,5′-dideoxy-D-threo- thymidine)platinum(II)). Detailed in vitro studies on the apoptosis pathway in lymphoma (BJAB), leukemia (NALM-6), and melanoma cells (Mel-HO) as well as on transfected or resistant cell lines were carried out. Thymiplatin significantly induced an apoptotic response, which was found to be associated with the loss of mitochondrial membrane potential and with caspase activation. The activity was shown to be independent of Fas-associated protein with death domain (FADD), but dependent on Bcl-2 expression. As a consequence, for thymiplatin a mitochondrial mode of action could be assigned. Moreover, the compound showed activity in cells resistant to common drugs, such as daunorubicin and vincristin, and showed synergistic effects with doxorubicin, vincristin, cytarabin, and daunorubicin. Prove your metal: Cisplatin analogues with platinum(II) and palladium(II) complexes based on 3′,5′-diamino thymidines were synthesized (see figure for an example) and one was found to induce apoptosis mediated by caspase-9 and -3 processing. Thymiplatin was proven to be active on cisplatin, vincristin and daunorubicin resistant leukemia cells, and was synergistic with cytarabin, vincristin, daunorubicin, and doxorubicin in lymphoma cells. Copyright
Deoxynucleic Guanidines (DNG)- Modified Oligonucleotides and Methods of Synthesizing Deoxynucleic Guanidine Strands
-
, (2021/01/22)
Disclosed herein are spherical nucleic acids (SNAs) comprising oligonucleotides comprising one or more modified oligonucleotides, and methods of use thereof. Also disclosed are methods of synthesizing modified oligonucleotides for use in therapeutics, inc
Mercury-Free Automated Synthesis of Guanidinium Backbone Oligonucleotides
Skakuj, Kacper,Bujold, Katherine E.,Mirkin, Chad A.
, p. 20171 - 20176 (2020/01/02)
A new method for synthesizing deoxynucleic guanidine (DNG) oligonucleotides that uses iodine as a mild and inexpensive coupling reagent is reported. This method eliminates the need for the toxic mercury salts and pungent thiophenol historically used in me
Synthesis of 3′,5′-dithiothymidine and related compounds
Eleuteri, Alessandra,Reese, Colin B.,Song, Quanlai
, p. 2237 - 2240 (2007/10/03)
When 3′,5′-di-O-mesylthymidine 7 is heated first with Methylamine in ethanol solution and then with the sodium salt of 4-methoxyphenylmethanethiol 9 in N,N-dimethylacetamide (DMA) solution, the bis(sulfide) 11a is obtained in high yield; when the dimesyl
Nucleoside Sultones: Synthons for the Preparation of Novel Nucleotide Analogues. 1. Synthesis and Ring-Opening Reactions
Crooks, Peter A.,Reynolds, Robert C.,Maddry, Joseph A.,Rathore, Anita,Akhtar, M. Shamim,et al.
, p. 2830 - 2835 (2007/10/02)
Treatment of either the 5'-O-tosyl or the 5'-O-mesyl derivative of 3'-O-mesylthymidine with lithium acetylide-ethylenediamine complex in DMSO affords the intramolecular 6,3-ester of 1,2,5,6-tetradeoxy-1-(3,4-dihydro-5-methyl-2,4-dioxo-1(2H)-pyrimidinyl)-β-D-erythro-hexofuranuronosulfonic acid (2).Similarly, the 5'-O-tosyl or 5'-O-mesyl derivative of 1-(2-deoxy-3-O-mesyl-β-D-threo-pentofuranosyl)thymine affords the intramolecular 6,3-ester of 1,2,5,6-tetradeoxy-1-(3,4-dihydro-5-methyl-2,4-dioxo-1(2H)-pyrimidinyl)-β-D-threo-hexofuranuronosulfonic acid (5).Sultone 5 reacts with a variety of nucleophiles to afford good yields of the corresponding 3'-substituted sulfonate salts (6, 7, 9, and 10) and, in some cases, the unsaturated nucleoside 8.Sultone 2 was generally much less susceptible to ring opening by nucleophiles.However, in the presence of base, nucleophilic substitution with azide ion did proceed via the intermediate anhydronucleoside, 11, to afford 6.Reaction of 2 with EtOH-NaOH afforded a 1:1 mixture of the epimeric 3'-hydroxy compounds 9 and 12.The above sulfonate salts represent interesting new isosteres of nucleoside 5'-O-phosphates.
N.M.R. Spectroscopical Investigations on the Conformational Behaviour of Some 2'- and 3'-Halogen-substituted Pyrimidine Nucleosides
Joecks, A.,Koeppel, H.,Schleinitz, K. D.,Cech, D.
, p. 881 - 892 (2007/10/02)
A series of 2'- and 3'-halogenated pyrimidine nucleosides has been synthesized and investigated by 1H, 13C and 19F n.m.r. spectroscopy.The 1H and 13C chemical shifts for the positions 2' and 3' depend linearly but oppositely on the substituent electronegativities XR.The conformational equilibrium N S of the nucleosides in solution is determined.An approximately linear correlation between the prefered gauche-gauche interaction of the exocyclic CH2OH groups and the ribose N conformation has been found.
