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Biomedical subjects

Satoshi Ichikawa

Publications and source records attributed to Satoshi Ichikawa.

16 recordsLinked to original sources
PubMed2025

Ozonated olive oil inhibits melanoma proliferation by inducing ferroptosis.

Although ozone is a potent oxidant that can damage lungs and skin after prolonged exposure, ozonated olive oil (OZO) exhibits antimicrobial, anti-inflammatory, and wound-healing effects. Here, we describe a novel application of OZO in melanoma therapy. Treatment with OZO markedly inhibited the proliferation of both human and murine melanoma cells, while sparing normal human keratinocyte. At the molecular level, OZO upregulated ferroptosis-related genes, decreased intracellular glutathione (GSH) and GPX4 protein levels and accelerated lipid peroxidation. Critically, OZO-induced growth inhibition in melanoma cells was prevented by ferroptosis inhibitors (ferrostatin-1 and deferiprone), but not by inhibitors of apoptosis or necroptosis. Taken together, these findings offer new therapeutics strategy for treating melanoma by inducing ferroptosis.

Ferroptosis↗
PubMed2006

Synthesis of 3'-beta-carbamoylmethylcytidine (CAMC) and its derivatives as potential antitumor agents.

3'-beta-Carbamoylmethylcytidine (CAMC) and its derivatives were synthesized using an intramolecular Reformatsky-type reaction promoted by SmI2 as the key step. In vitro tumor cell growth inhibitory activity was evaluated and CAMC was found to exhibit potent cytotoxicity against various human tumor cell lines. From a structure-activity relationship study it was postulated that the cytotoxic mechanism of action of CAMC did not require phosphorylation at the 5'-hydroxyl group. This study provides a novel strategy for the development of a new type of antitumor nucleoside.

Antineoplastic Agents↗
PubMed2006

[Synthetic study of nucleoside antibiotics].

Some of nucleoside antibiotics include complex structures as well as sensitive functionality, which are challenging targets for organic chemists. Among complex nucleoside antibiotics, there are also good drug candidates because they possess a variety of interesting biological properties. Herbicidin B and fully protected tunicaminyluracil, which were undecose nucleoside antibiotics, were synthesized using a samarium diiodide (SmI(2)) mediated aldol reaction with the use of alpha-phenylthioketones as enolate sources. The characteristics of the SmI(2)-mediated aldol reaction are that the enolate can be regioselectively generated and the aldol reaction proceeds under near neutral condition. This reaction is proved to be a powerful reaction for the synthesis of complex nucleoside antibiotics. The synthesis of caprazol, the core structure of caprazamycins, was conducted by the strategy including beta-selective ribosylation without using a neighboring group participation and the construction of a diazepanone by a modified reductive amination. Our synthetic route would provide a range of key analogues with partial structures to define the pharmacophore, which can be a lead for the development of more effective anti-bacterial agents.

Anti-Bacterial Agents↗
PubMed2005

Synthesis of stable and cell-type selective analogues of cyclic ADP-ribose, a Ca(2+)-mobilizing second messenger. Structure--activity relationship of the N1-ribose moiety.

We previously developed cyclic ADP-carbocyclic ribose (cADPcR, 2) as a stable mimic of cyclic ADP-ribose (cADPR, 1), a Ca(2+)-mobilizing second messenger. A series of the N1-ribose modified cADPcR analogues, designed as novel stable mimics of cADPR, which were the 2"-deoxy analogue 3, the 3"-deoxy analogue 4, the 3"-deoxy-2"-O-(methoxymethyl) analogue 5, the 3"-O-methyl analogue 6, the 2",3"-dideoxy analogue 7, and the 2",3"-dideoxydidehydro analogue 8, were successfully synthesized using the key intramolecular condensation reaction with phenylthiophosphate-type substrates. We investigated the conformations of these analogues and of cADPR and found that steric repulsion between both the adenine and N9-ribose moieties and between the adenine and N1-ribose moieties was a determinant of the conformation. The Ca(2+)-mobilizing effects were evaluated systematically using three different biological systems, i.e., sea urchin eggs, NG108-15 neuronal cells, and Jurkat T-lymphocytes. The relative potency of Ca(2+)-mobilization by these cADPR analogues varies depending on the cell-type used: e.g., 3"-deoxy-cADPcR (4) > cADPcR (2) > cADPR (1) in sea urchin eggs; cADPR (1) >> cADPcR (2) approximately 3"-deoxy-cADPcR (4) in T-cells; and cADPcR (2) > cADPR (1) > 3"-deoxy-cADPcR (4) in neuronal cells, respectively. These indicated that the target proteins and/or the mechanism of action of cADPR in sea urchin eggs, T-cells, and neuronal cells are different. Thus, this study represents an entry to cell-type selective cADPR analogues, which can be used as biological tools and/or novel drug leads.

Animals↗
PubMed2005

Synthesis of complex nucleoside antibiotics.

Herbicidin B and fully prtected tunicaminyluracil, which were undecose nucleoside antibiotics, were synthesized using a samarium diiodide (SmI2) mediated aldol reaction with the use of alpha-phenylthioketone as an enolate. The characteristics of the SmI2-mediated aldol reaction are that the enolate can be regioselectively generated and the aldol reaction proceeds under near neutral condition. This reaction is proved to be a powerful reaction for the synthesis of complex nucleoside antibiotics. The synthesis of caprazol, the core structure of caprazamycins, was conducted by the strategy including beta-selective ribosylation without using a neighboring group participation and the construction of a diazepanone by a modified reductive amination. Our synthetic route would provide a range of key analogues with partial structures to define the pharmacophore, which can be a lead for the development of more effective anti-bacterial agents.

Adenosine↗
PubMed2005

[A case of ascities decrease in malignant peritoneal mesothelioma by weekly intra-peritoneal administration of cisplatin and paclitaxel].

We report a case of malignant peritoneal mesothelioma (MPM) in a 63-year-old man. He had body weight loss and abdominal distension for one month, and was admitted to our hospital. Abdominal sonography showed a large mass occupying the right lower abdomen and an existence of a lot of ascites. Computed tomography and magnetic resonance image showed a lot of ascites and omentum cake. Cytology of the ascites was Class V but its histological classification was unknown. Then we performed biopsy of the tumor into the omentum with abdominal sonography. The histological diagnosis was MPM because the tumor cells showed positive for calretinin. He received a combination chemotherapy of weekly intra-peritoneal administration of cisplatin (70 mg/ day) and paclitaxel (100 mg/day). The ascites was decreased and per os (PO) was possible, but omentum cake was not changed. MPM was poor in prognosis and the control of ascites was difficult. We suggest that the chemotherapy of intra-peritoneal administration was a better procedure than others to control ascites with malignant tumors.

Antineoplastic Agents↗
PubMed2004

Oligodeoxynucleotides having a loop consisting of 3'-deoxy-4'-C-(2-hydroxyethyl)thymidines form stable hairpins.

Components that form stable hairpin loops are highly useful for the development of functional DNA and RNA molecules. We have designed and synthesized a sugar-modified thymidine analogue, 3'-deoxy-4'-C-(2-hydroxyethyl)thymidine (X), as a nucleosidic loop component stabilizing the hairpin structure. The ODNs I-1-4, 5'-d[CGAACG-X(n)-CGTTCG]-3' (I-1, n = 1; I-2, n = 2; I-3, n = 3; I-4, n = 4), forming the hairpin loop structures, of which the loop moiety consisted of the analogue X, and also the corresponding unmodified ODNs II-1-4, 5'-d[CGAACG-T(n)-CGTTCG]-3' (II-1, n = 1; II-2, n = 2;II-3, n = 3; II-4, n = 4), having a thymidine loop, were synthesized by the phosphoramidite method. The melting temperatures (T(m)) of the ODNs I-1-4 containing X in the loop moiety at 5 microM were 67.1, 68.1, 73.0, and 69.3 degrees C, respectively, and those of the control natural ODNs II-1-4 were 65.3, 67.0, 69.2, and 68.8 degrees C, respectively. Thus, the ODNs I-1-4 formed a more thermally stable hairpin than the corresponding unmodified ODNs II-1-4 having an equal number of loop residues. The hairpin structures of the modified ODNs I-1-4 and the unmodified ODNs II-1-4 were investigated by CD spectroscopy and molecular mechanics calculations. These results showed that the 4'-branched nucleoside X can stabilize hairpin structures when it is present in the loop moiety, probably due to the flexibility of the one-carbon-elongated 4'-branched structure.

Base Pairing↗
PubMed2004

Synthesis of tunicaminyluracil derivatives.

A tunicaminyluracil derivative, which is a key component of the tunicamycin nucleoside antibiotics, was synthesized using a samarium diiodide (SmI2) mediated aldol reaction and intramolecular Pummerer reaction as the key steps. The alpha-phenylthio ketone 11, the precursor of the samarium enolate, was prepared from D-galactose. Treatment of 11 with SmI2 at -40 degrees C resulted in complete conversion to the corresponding samarium enolate, and subsequent addition of uridine 5'-aldehyde 12 afforded the desired aldol products 13a,b. Compound 13a was converted to the sulfoxide 15 by a sequential diastereoselective reduction of the ketone and an oxidation with mCPBA. Activation of 15 with Tf2O provided the desired cyclized compound 17. In this reaction, the aldol product 13a was also obtained as a consequence of a competitive intramolecular version of DMSO-oxidation via a 7-membered ring intermediate. Compound 18 or 19 are ready for use as a glycosyl donor in glycosylations to provide a range of analogues as potential glycosyltransferase inhibitors as well as related natural products.

Anti-Bacterial Agents↗
PubMed2003

Fundamental role of the fostriecin unsaturated lactone and implications for selective protein phosphatase inhibition.

Key derivatives and analogues of fostriecin were prepared and examined that revealed a fundamental role for the unsaturated lactone and confirmed the essential nature of the phosphate monoester. Thus, an identical 200-fold reduction in protein phosphatase 2A (PP2A) inhibition is observed with either the saturated lactone (7) or with an analogue that lacks the entire lactone (15). This 200-fold increase in PP2A inhibition attributable to the unsaturated lactone potentially may be due to reversible C269 alkylation within the PP beta12-beta13 active site loop accounting for PP2A/4 potency and selectivity.

Alkenes↗
PubMed2003

The first radical method for the introduction of an ethynyl group using a silicon tether and its application to the synthesis of 2'-deoxy-2'-C-ethynylnucleosides.

A novel radical method for the stereoselective introduction of an ethynyl group has been developed. When a solution of ethynyldimethylsilyl (EDMS) or [2-(trimethylsilyl)ethynyl]dimethylsilyl (TEDMS) ethers of trans-2-iodoindanol was treated with Et(3)B followed by tetrabutylammonium fluoride in toluene, atom transfer 5-exo-cyclization and subsequent elimination occurred to give cis-2-ethynylindanol in high yield. The method was shown to be useful in the introduction of an ethynyl group in various five- and six-membered-ring iodohydrins. Furthermore, 2'-deoxy-2'-C-ethynyluridine (6) and -cytidine (7), which were designed as novel antimetabolites, were readily synthesized by using this method as the key step. This would be the first example in which a radical reaction was used for introducing an ethynyl group.

Chemistry, Organic↗
PubMed2003

Electron holographic 3-D nano-analysis of Au/TiO2 catalyst at interface.

Three-dimensional (3-D) nanostructures of gold catalysts supported on TiO2 were analysed by electron holography and high-resolution electron microscopy. The contact angle of the gold particle on TiO2 tended to be >90 degrees in the case of gold particles with a size (height) of >4 nm and it tended to be <90 degrees for gold particles with a height of <2 nm. The change in morphology increases the perimeter at the Au/TiO2 interface as the particle size decreases. This change in 3-D structure should be attributed to a change in electronic structure at the interface. It was found that electron holography enabled 3-D analysis at the atomic level and was effective for analysing nanostructured particles.

Journal Article↗
PubMed2002

A highly stereoselective samarium diiodide-promoted aldol reaction with 1'-phenylseleno-2'-keto nucleosides. Synthesis of 1'alpha-branched uridine derivatives.

Since 1'-branched nucleosides are biologically important targets in medicinal chemistry, more efficient methods for preparing them are required. The 1'alpha-branched uridine derivatives were successfully synthesized via a samarium diiodide (SmI(2))-promoted aldol reaction. Treatment of the 1'alpha-phenylseleno-2'-ketouridine derivative 6, readily prepared from uridine, with SmI(2) at -78 degrees C in THF reductively cleaved the anomeric Se-C bond to generate the corresponding samarium enolate, which was highly stereoselectively condensed with aldehydes, such as PhCHO, MeCHO, i-PrCHO, or (CH(2)O)(n)(), to give the corresponding 1'alpha-1' 'S-branched products 12a-d. This is the first time an enolate has been generated by reductively cleaving a C-Se bond. The highly selective stereochemical results suggest that the aldol reaction proceeds via a chelation-controlled transition state. When an excess of aldehyde was used and the reaction mixture was gradually warmed, the tandem aldol-Tishchenko reaction proceeded to give the "arabino-type" nucleosides 14a-c, having a 2'-"up" hydroxyl and 1'alpha-1' 'S-branched chain. 1'alpha-Hydroxymethyluridine (21), which is the uracil version of the antitumor antibiotic angustmycin C, was synthesized from the aldol reaction product 10.

Aldehydes↗
PubMed2002

Synthesis of a novel mesoporous tin phosphate, SnPO4.

Novel mesoporus tin phosphates have been synthesized using alkyltrimethylammonium bromide (alkyl = C8-C18) as surfactant; the structure of the materials is stable at 500 degrees C. UV-VIS spectra show tetrahedral coordination of tin.

Journal Article↗
PubMed1998

Stereo- and Regioselective Introduction of 1- or 2-Hydroxyethyl Group via Intramolecular Radical Cyclization Reaction with a Novel Silicon-Containing Tether. An Efficient Synthesis of 4'alpha-Branched 2'-Deoxyadenosines(1).

An efficient method for the synthesis of 4'alpha-branched 2'-deoxyadenosines starting from 2'-deoxyadenosine has been developed utilizing a novel radical cyclization reaction with a silicon tether. The radical reaction of 4'beta-(phenylseleno)-3'-O-diphenylvinylsilyl adeninenucleoside derivative 17 with Bu(3)SnH and AIBN, followed by Tamao oxidation, gave selectively either the 4'alpha-(2-hydroxyethyl) derivative 21 or 4'alpha-(1-hydroxyethyl) derivative 19, depending on the reaction conditions. With a lower Bu(3)SnH concentration, the reaction gave the 4'alpha-(2-hydroxyethyl) derivative 21, via a 6-endo-radical cyclized product 20, as the sole product in 72% yield. The reaction of 17 in the presence of excess Bu(3)SnH gave 19 quantitatively, via a 5-exo-cyclized product 18, as a diastereomeric mixture. The reaction mechanism was examined using Bu(3)SnD. The results demonstrated that the 5-exo cyclized (3-oxa-2-silacyclopentyl)methyl radical (C) was formed initially which was trapped when the concentration of Bu(3)SnH(D) was high enough. With lower concentrations of Bu(3)SnH(D), radical C rearranged into the ring-enlarged 4-oxa-3-silacyclohexyl radical (D) which was then trapped with Bu(3)SnH(D) to give endo-cyclized product F.

Journal Article↗