Cytotoxicity and Pharmacokinetics of 1-.BETA.-D-Arabinofuranosyl-2-thiocytosine, a 2-Sulphur Substituted Derivative of Cytarabine.

Kawaguchi, Takeo; Ichikawa, Tomohisa; Hasegawa, Tetsuya; Saneyoshi, Mineo; Yukita, Ayako; Asano, Makoto; Wakayama, Toshiyuki; Kato, Hisatoyo; Nagata, Toshiyuki

doi:10.1248/bpb.22.100

Cited by 4 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The antileukemic activity of fluorinated 2-TC has been proven only recently [10]. Numerous substituted 2-TC derivatives, including 1-(β- D -arabinofuranosyl)-2-thiocytosine and its analogs and complexes with trimethylplatinum have been synthesized, and their enzymatic reactivities and antitumor activities have been studied [11–13]. The cytotoxic activities of some of them were found to be even higher than that of cisplatin, and they were even active against cisplatin-resistant cell lines [13].…”

Section: Introductionmentioning

confidence: 99%

A comparative study of the hydrogen-bonding patterns and prototropism in solid 2-thiocytosine (potential antileukemic agent) and cytosine, as studied by 1H-14N NQDR and QTAIM/ DFT

et al. 2011

View full text Add to dashboard Cite

A potential antileukemic and anticancer agent, 2-thiocytosine (2-TC), has been studied experimentally in the solid state by 1H-14N NMR-NQR double resonance (NQDR) and theoretically by the quantum theory of atoms in molecules (QTAIM)/density functional theory (DFT). Eighteen resonance frequencies on 14N were detected at 180 K and assigned to particular nitrogen sites (−NH2, –N=, and –NH–) in 2-thiocytosine. Factors such as the nonequivalence of molecules (connected to the duplication of sites) and possible prototropic tautomerism (capable of modifying the type of site due to proton transfer) were taken into account during frequency assignment. The result of replacing oxygen with sulfur, which leads to changes in the intermolecular interaction pattern and molecular aggregation, is discussed. This study demonstrates the advantages of combining NQDR and DFT to extract detailed information on the H-bonding properties of crystals with complex H-bonding networks. Solid-state properties were found to have a profound impact on the stabilities and reactivities of both compounds.FigureThe experimental 1H-14N NQDR spectrum of 2-thiocytosine obtained at T = 180 K by the solid effect technique (left) and 3d distribution of the electron density Laplacian calculated by DFT (right)

show abstract

Section: Introductionmentioning

confidence: 99%

A comparative study of the hydrogen-bonding patterns and prototropism in solid 2-thiocytosine (potential antileukemic agent) and cytosine, as studied by 1H-14N NQDR and QTAIM/ DFT

et al. 2011

View full text Add to dashboard Cite

show abstract

“…It is interesting to note that cytotoxic activity of the substituted 2thiocytosines coordinated with organoplatinum compounds was found to be higher than that of platinum derivative itself, in particular, cisplatin. [32][33][34]…”

Section: Nmr Ag + Cation Complexation Studiesmentioning

confidence: 99%

“…26 It should be noted that uracil as well as 5-methyluracil (thymine) moieties enter into the composition of the nucleic acids of RNA and DNA, and 2-thiocytosine is known as a modied nucleobase found in the tRNA of some organisms. 27 It was also reported that 2-thiocytosine and its derivatives as well as their complexes possess antileukemic, 28,29 anticancer, 30,31 antitumor, [32][33][34] antiviral 35 and antimycobacterial 36 activities.…”

Section: Introductionmentioning

confidence: 99%

Metal binding properties of pyrimidinophanes and their acyclic counterparts

et al. 2014

View full text Add to dashboard Cite

A series of acyclic and macrocyclic nucleobase derivatives that contain uracil and 2-thiocytosine units linked by polymethylene spacers was prepared. The length of spacers as well as the oxidation number of sulfur atoms entering into the structure of the compounds was varied. The crystal structure of pyrimidinophane with hexa-and heptamethylene linkers was established by X-ray analysis. The metal ion-binding properties of pyrimidinophanes and their acyclic counterparts were investigated by liquid extraction and 1 H NMR titration experiments. The compounds with 2-thiocytosine fragments revealed a high selectivity of extraction towards Ag + ions. The stoichiometry of silver complexes and the binding constants have been determined. The antibacterial activity of these complexes was also discussed.

show abstract

“…5 In fact, TC and its derivatives along with their coordination complexes were reported to have potent anti-leukemic and antitumor properties. [6][7][8][9] Compound TU has been employed for the diagnosis and chemotherapy of disseminated melanoma and exhibits antivirus and antitumor activities. [10][11][12] Also, TU is a selective inhibitor of neuronal nitric oxide synthase which catalyzes the NADPH -dependent formation of nitric oxide from Larginine and molecular oxygen.…”

Section: Introductionmentioning

confidence: 99%

Contrasting reactions of hydrated electron and formate radical with 2-thio analogues of cytosine and uracil

Prasanthkumar

Álvarez-Idaboy

Kumar

et al. 2016

Phys. Chem. Chem. Phys.

View full text Add to dashboard Cite

2-Thiocytosine (TC) and 2-thiouracil (TU) were subjected to hydrated electron (e), formate radical (CO˙) and 2-hydroxypropan-2-yl radical ((CH)˙COH) reactions in aqueous medium. Transients were characterized by absorption spectroscopy and the experimental findings were rationalized by DFT calculations at LC-ωPBE and M06-2X levels using a 6-311+G(d,p) basis set and SMD solvation. In e reactions, a ring N-atom protonated radical of TC and an exocyclic O-atom protonated radical of TU were observed via addition of e and subsequent protonation by solvent molecules. However, two competing but simultaneous mechanisms are operative in CO˙ reactions with TC and TU. The first one corresponds to formations of N(O)-atom protonated radicals (similar to e reactions); the second mechanism led to 2 center-3 electron, sulfur-sulfur bonded neutral dimer radicals, TCdim˙ and TUdim˙. DFT calculations demonstrated that H-abstraction by CO˙ from TC(TU) results in S-centered radical which upon combination with TC(TU) provide the dimer radical. In some cases, DFT energy profiles were further validated by CBS-QB3//M06-2X calculations. This is the first time report for a contradictory behavior in the mechanisms of e and CO˙ reactions with any pyrimidines or their thio analogues.

show abstract

Cytotoxicity and Pharmacokinetics of 1-.BETA.-D-Arabinofuranosyl-2-thiocytosine, a 2-Sulphur Substituted Derivative of Cytarabine.

Cited by 4 publications

References 0 publications

A comparative study of the hydrogen-bonding patterns and prototropism in solid 2-thiocytosine (potential antileukemic agent) and cytosine, as studied by 1H-14N NQDR and QTAIM/ DFT

A comparative study of the hydrogen-bonding patterns and prototropism in solid 2-thiocytosine (potential antileukemic agent) and cytosine, as studied by 1H-14N NQDR and QTAIM/ DFT

Metal binding properties of pyrimidinophanes and their acyclic counterparts

Contrasting reactions of hydrated electron and formate radical with 2-thio analogues of cytosine and uracil

Contact Info

Product

Resources

About