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1.
Anticancer Res ; 40(1): 379-386, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892590

RESUMO

BACKGROUND/AIM: We evaluated the efficacy and safety of carbon-ion radiotherapy (CIRT) alone for Stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Data of 65 patients (median age=73 years) with Stage III NSCLC who underwent CIRT alone in the QST Hospital, Chiba, Japan, between 1997 and 2015 were retrospectively analysed. The median dose was 72.0 Gy (relative biological effectiveness). RESULTS: The median follow-up was 27.6 months (range=1.6-207.7 months). Two-year local control, progression-free survival (PFS), and overall survival (OS) rates were 73.9%, 38.6%, and 54.9%, respectively. Overall, 1 (2%), 4 (6%), and 1 (2%) patient developed Grade 4 (mediastinal haemorrhage), Grade 3 (radiation pneumonitis), and Grade 3 (bronchial fistula) toxicities, respectively. On univariate analysis, clinical T and N stage and CIRT timing were significant predictors of PFS and OS; clinical target volume was a significant predictor of PFS. CONCLUSION: CIRT alone is effective with acceptable toxicity for Stage III NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Radioterapia com Íons Pesados/efeitos adversos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Resultado do Tratamento
2.
ACS Omega ; 4(5): 9029-9040, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31459991

RESUMO

4,6-Dihydroxysalicylic acid was activated under air to catalyze the one-pot oxidative condensation reaction of benzylamines with acetophenones in the presence of BF3·Et2O, affording 2,4,6-trisubstituted pyridines in yields of 59-91%. During this metal-free oxidative condensation reaction, the benzylamines not only provided the aryl moiety at the 4-position of the pyridines but also acted as the nitrogen donor. This method can be applied to the metal-free synthesis of G-quadruplex binding ligands by the sequential addition of 4-chlorobutyryl chloride and pyrrolidine to the reaction system of the 2,4,6-trisubstituted pyridine synthesis.

3.
J Org Chem ; 84(18): 11562-11571, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31432673

RESUMO

Metal-free, oxidative four-component Ugi reactions (U-4CRs) were conducted to synthesize dipeptides from two different amines, isocyanides, and carboxylic acids using 2,4,6-trihydroxybenzoic acid catalyst in O2 atmosphere. The organocatalytic U-4CRs proceed via oxidative cross-coupling of benzylamines with other aliphatic or aromatic amines to form imines, followed by condensation with isocyanides and carboxylic acids. The U-4CRs via cross-coupling of amines are rare, and the simple, metal-free procedures are advantageous for further applications in drug and heterocycle syntheses.

4.
J Org Chem ; 84(18): 11741-11751, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31432680

RESUMO

Using tetraaryllead compounds (PbAr4) as arylating reagents, isocyanides undergo selective diarylation in the presence of palladium catalysts such as Pd(OAc)2 or Pd(PPh3)4 to afford imines and/or α-diimines based on the isocyanide employed. With aliphatic isocyanides, imines are obtained preferentially, whereas α-diimines are formed in the case of electron-rich aromatic isocyanides. The differences in imine/α-diimine selectivity can be attributed to the stability of imidoylpalladium intermediates formed in this catalytic reaction. Compared with other arylating reagents, tetraaryllead compounds are excellent candidates for use in the selective transformations to imines and/or α-diimines, especially in terms of inhibiting the oligomerization of isocyanides, which results in a lower product selectivity in many transition-metal-catalyzed reactions of isocyanides.

5.
Anticancer Res ; 39(8): 4199-4206, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366506

RESUMO

BACKGROUND/AIM: We previously synthesized a glucose-conjugated chlorin compound e6 (G-chlorin e6), and reported that it has very strong antitumor effects. The aim of the present study was to synthesize acetylated glucose-conjugated chlorin (AcN003HP) and evaluate its antitumor effect and excretion. MATERIALS AND METHODS: To evaluate the antitumor effect of AcN003HP, its IC50 was calculated as well as its accumulation in cancer cells was examined by flow cytometry. Confocal microscopy was used to observe the intracellular localization of AcN003HP. The excretion and antitumor effects of AcN003HP were also evaluated in vivo. RESULTS: AcN003HP showed stronger antitumor effects and accumulation into cancer cells compared to talaporfin sodium, a conventional photosensitizer. AcN003HP was localized in the endoplasmic reticulum. In a xenograft tumor mouse model, AcN003HP showed longer excretion time from the body than G-chlorin e6, and photodynamic therapy using AcN003HP showed very strong antitumor effects. CONCLUSION: The safety, improved controllability, and robust antitumor effects suggest AcN003HP as a good next-generation photosensitizer.


Assuntos
Neoplasias Gastrointestinais/terapia , Glucose/administração & dosagem , Fotoquimioterapia , Fármacos Fotossensibilizantes/administração & dosagem , Acetilação/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Retículo Endoplasmático/efeitos dos fármacos , Citometria de Fluxo , Neoplasias Gastrointestinais/patologia , Glucose/síntese química , Glucose/química , Humanos , Camundongos , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Porfirinas/administração & dosagem , Porfirinas/síntese química , Porfirinas/química , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Cancers (Basel) ; 11(5)2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31071967

RESUMO

By using the Warburg effect-a phenomenon where tumors consume higher glucose levels than normal cells-on cancer cells to enhance the effect of photodynamic therapy (PDT), we developed a new photosensitizer, glucose-conjugated chlorin e6 (G-Ce6). We analyzed the efficacy of PDT with G-Ce6 against canine mammary carcinoma (CMC) in vitro and in vivo. The pharmacokinetics of G-Ce6 at 2, 5, and 20 mg/kg was examined in normal dogs, whereas its intracellular localization, concentration, and photodynamic effects were investigated in vitro using CMC cells (SNP cells). G-Ce6 (10 mg/kg) was administered in vivo at 5 min or 3 h before laser irradiation to SNP tumor-bearing murine models. The in vitro study revealed that G-Ce6 was mainly localized to the lysosomes. Cell viability decreased in a G-Ce6 concentration- and light intensity-dependent manner in the PDT group. Cell death induced by PDT with G-Ce6 was not inhibited by an apoptosis inhibitor. In the in vivo study, 5-min-interval PDT exhibited greater effects than 3-h-interval PDT. The mean maximum blood concentration and half-life of G-Ce6 (2 mg/kg) were 15.19 ± 4.44 µg/mL and 3.02 ± 0.58 h, respectively. Thus, 5-min-interval PDT with G-Ce6 was considered effective against CMC.

7.
Lancet Oncol ; 20(5): 674-685, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30885458

RESUMO

BACKGROUND: The risk of subsequent primary cancers in patients with prostate cancer after treatment with photon radiotherapy is small in absolute numbers, but it is higher than that after surgical treatment. Carbon ion radiotherapy has a theoretically lower risk of inducing secondary malignancies than photon radiotherapy, but this risk has not been investigated in practice because of the low number of facilities offering such therapy worldwide and the limited data on long-term follow-up because the therapy has only been available since 1994. We aimed to analyse the risk of subsequent primary cancers after treatment with carbon ion radiotherapy in patients with localised prostate cancer and to compare it with that after photon radiotherapy or surgery in this setting. METHODS: In this retrospective cohort study, we reviewed records of patients who received carbon ion radiotherapy for prostate cancer between June 27, 1995, and July 10, 2012, at the National Institute of Radiological Sciences (NIRS) in Japan. We also retrieved the records of patients diagnosed and treated for prostate cancer between Jan 1, 1994, and Dec 31, 2012, from the Osaka Cancer Registry. Eligible patients had histologically confirmed localised prostate cancer and a minimum follow-up of at least 3 months; no age restrictions were applied. We excluded patients with metastasis, node-positive disease, or locally invasive (T4 stage) prostate cancer, those with previous or synchronous malignancies, and those who received previous radiotherapy or chemotherapy. We did a multivariable analysis to estimate predictors of subsequent cancers after carbon ion radiotherapy treatment. We also used propensity score inverse probability weighting to retrospectively compare the incidence of subsequent cancers in patients with localised prostate cancer treated with carbon beams, photon radiotherapy, or surgery. FINDINGS: Of 1580 patients who received carbon radiotherapy for prostate cancer at the NIRS, 1455 (92%) patients met the eligibility criteria. Of 38 594 patients with prostate cancer identified in the Osaka registry, 1983 (5%) patients treated with photon radiotherapy and 5948 (15%) treated with surgery were included. Median follow-up durations were 7·9 years (IQR 5·9-10·0) for patients who received carbon ion radiotherapy (after limiting the database to 10-year maximum follow-up), 5·7 years (4·5-6·4) for patients who received photon radiotherapy, and 6·0 years (5·0-8·6) for those who received surgery. 234 subsequent primary cancers were diagnosed in the carbon ion radiotherapy cohort; some patients developed several tumours. On multivariable analysis, age (p=0·0021 for 71-75 years vs ≤60 years; p=0·012 for >75 years vs ≤60 years) and smoking (p=0·0005) were associated with a higher risk of subsequent primary cancers in patients treated with carbon ion radiotherapy. In the propensity score-weighted analyses, carbon ion radiotherapy was associated with a lower risk of subsequent primary cancers than photon radiotherapy (hazard ratio [HR] 0·81 [95% CI 0·66-0·99]; p=0·038) or surgery (HR 0·80 [0·68-0·95]; p=0·0088), whereas photon radiotherapy was associated with a higher risk of subsequent primary cancers than surgery (HR 1·18 [1·02-1·36]; p=0·029). INTERPRETATION: Our analysis suggests that patients with localised prostate cancer treated with carbon ion radiotherapy appear to have a lower risk of subsequent primary cancers than those treated with photon radiotherapy. Although prospective evaluation with longer follow-up is warranted to support these results, our data supports a wider adoption of carbon ion radiotherapy for patients with expected long-term overall survival or those with poor outcomes after receiving conventional treatments. FUNDING: Research Project for Heavy Ions at the National Institute of Radiological Sciences (Japan).

8.
Chemistry ; 25(27): 6797-6806, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-30848860

RESUMO

The facile synthesis of organophosphorus compounds is of great importance for the development of new synthetic methods by using air-stable sources of phosphorus. In this respect, a synthetic method that is based on a reductive rearrangement and is capable of converting air-stable pentavalent phosphorus compounds into reactive trivalent phosphorus compounds is a powerful tool. Tetraphenyldiphosphine disulfide, which is a shelf-stable solid, was the focus of this study, and it was shown to undergo reductive rearrangement to trigger the bisthiophosphinylation of a variety of alkenes, such as terminal, cyclic, internal, and branched alkenes, 1,3-dienes, and terminal alkynes when exposed to light without any catalyst, base, or additive.

9.
Cancer Sci ; 110(2): 734-741, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30467928

RESUMO

The efficacy and safety of carbon-ion radiotherapy (CIRT) for locally advanced non-small-cell lung cancer (LA-NSCLC) remain unclear. We reported the clinical outcomes of CIRT for LA-NSCLC. Data for 141 eligible patients who received CIRT between 1995 and 2015 were retrospectively analyzed. Local control (LC), locoregional control (LRC), progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. The median age was 75.0 years. Overall, 21 (14.9%), 57 (40.4%), 43 (30.5%) and 20 (14.2%) patients had T1, T2, T3 and T4 disease, respectively. Moreover, 51 (36.2%), 45 (31.9%), 40 (28.4%) and 5 (3.5%) patients had N0, N1, N2 and N3 disease, respectively. Furthermore, 34 (24.1%), 42 (29.8%), 45 (31.9%) and 20 (14.2%) patients had stages IIA, IIB, IIIA and ΙΙΙB disease, respectively. Overall, 62 (44.0%), 60 (42.6%), 8 (5.7%) and 11 (7.8%) patients had adenocarcinoma, squamous cell carcinoma, large cell carcinoma, and others, respectively. The median dose was 72.0 Gy (relative biological effectiveness). No patient received concurrent chemotherapy. Median follow-up periods were 29.3 (1.6-207.7) and 40.0 (10.7-207.7) months for all patients and survivors, respectively. Two-year LC, PFS and OS rates were 80.3%, 40.2% and 58.7%, respectively. Overall, 1 (0.7%), 5 (3.5%) and 1 (0.7%) patient developed Grades 4 (mediastinal hemorrhage), 3 (radiation pneumonitis) and 3 (bronchial fistula) toxicities, respectively. Multivariate analysis showed adenocarcinoma and N2/3 classification as significant poor prognosticators of PFS. CIRT is an effective treatment with acceptable toxicity for LA-NSCLC, especially for elderly patients or patients with severe comorbidities who cannot be treated with surgery or chemoradiotherapy.


Assuntos
Carbono/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia/métodos , Feminino , Radioterapia com Íons Pesados/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento
10.
Chemistry ; 25(9): 2295-2302, 2019 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-30398679

RESUMO

Bis-phosphanated compounds are regarded as the most ubiquitous privileged ligand structures in transition-metal catalysis. The development of highly atom economical reactions is of great importance for their syntheses because less atom economical methods often require complicated purification procedures under inert atmospheres to remove excess starting materials and byproducts. Herein, the photoinduced addition reactions of diphosphane monosulfides bearing PV (S)-PIII single bonds to alkenes is disclosed. These reactions require only equimolar amounts of the diphosphane monosulfide relative to the alkene and facilitate highly selective introduction of two different types of phosphorus-containing groups, such as thiophosphoryl and phosphanyl groups, into a variety of alkenes without any catalyst, base, or additive.

11.
Sci Adv ; 4(3): eaar3979, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29740603

RESUMO

Ultrasonic imaging has been implemented as a powerful tool for noninvasive subsurface inspections of both structural and biological media. Current ultrasound probes are rigid and bulky and cannot readily image through nonplanar three-dimensional (3D) surfaces. However, imaging through these complicated surfaces is vital because stress concentrations at geometrical discontinuities render these surfaces highly prone to defects. This study reports a stretchable ultrasound probe that can conform to and detect nonplanar complex surfaces. The probe consists of a 10 × 10 array of piezoelectric transducers that exploit an "island-bridge" layout with multilayer electrodes, encapsulated by thin and compliant silicone elastomers. The stretchable probe shows excellent electromechanical coupling, minimal cross-talk, and more than 50% stretchability. Its performance is demonstrated by reconstructing defects in 3D space with high spatial resolution through flat, concave, and convex surfaces. The results hold great implications for applications of ultrasound that require imaging through complex surfaces.


Assuntos
Imagem Tridimensional/instrumentação , Transdutores , Ultrassonografia/instrumentação , Desenho de Equipamento , Propriedades de Superfície
12.
J Org Chem ; 83(9): 5267-5273, 2018 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-29611704

RESUMO

Despite the availability of selective synthetic approaches to multifunctionalized substituted olefins, the cyanothiolation of internal alkynes has been much less explored. Herein, we show that nonactivated internal alkynes can be successfully cyanothiolated with diaryl disulfides and tert-butyl isocyanide in the presence of a Pd catalyst (e.g., Pd(PPh3)4) with the release of isobutene and arenethiol to afford ß-thiolated alkenyl cyanides in yields of 34-89%.

13.
Oper Neurosurg (Hagerstown) ; 14(4): 341-350, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29554374

RESUMO

BACKGROUND: Stereotactic radiosurgery (SRS) has been accepted as a therapeutic option for intracranial meningiomas; however, the detailed data on outcomes in elderly patients remain unclear. OBJECTIVE: To delineate the efficacy of SRS for meningiomas in elderly patients. METHODS: The outcomes of 67 patients aged ≥65 yr who underwent SRS for benign intracranial meningioma (World Health Organization grade I) between 1990 and 2014 at our institution were retrospectively analyzed. The median age was 71 yr (range, 65-83 yr), and the mean and median follow-up were 62 and 52 mo (range, 7-195 mo), respectively. Tumor margins were irradiated with a median dose of 16 Gy, and the median tumor volume was 4.9 cm3 (range, 0.7-22.9 cm3). RESULTS: Actuarial local tumor control rates at 3, 5, and 10 yr after SRS were 92%, 86%, and 72%, respectively. Previous surgery and parasagittal/falcine location were statistically significant predictive factors for failed tumor control. Mild or moderate adverse events were noted in 9 patients. No severe adverse event was observed. A higher margin dose was significantly associated with adverse events by univariate analysis. CONCLUSION: SRS is one of the standard therapies for meningiomas in elderly patients, providing both favorable tumor control and a low risk of adverse events under minimum invasiveness.


Assuntos
Neoplasias Meníngeas/radioterapia , Meningioma/radioterapia , Radiocirurgia/métodos , Idoso , Idoso de 80 Anos ou mais , Edema Encefálico/etiologia , Comorbidade , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Margens de Excisão , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
14.
Biochem Biophys Res Commun ; 496(4): 1204-1209, 2018 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-29408755

RESUMO

BACKGROUND: Photodynamic therapy (PDT) exploits the reaction between photosensitizer and irradiated light to generate potentially therapeutic reactive oxygen species such as singlet oxygen in cancer cells. We have reported several sugar-conjugated chlorins that express stronger antitumor effects in PDT than talaporfin sodium (TS), a second-generation photosensitizer clinically used in Japan. In this study, we developed a novel glucose-conjugated chlorin e6 (G-chlorin e6) and evaluated its antitumor effects. METHODS: G-chlorin e6 was synthesized with a core photosensitizer chlorin e6 conjugated to glucose. We measured the half maximal inhibitory concentration (IC50) to compare the PDT effects of G-chlorin e6 and TS, and flow cytometry was performed to examine the accumulation of G-chlorin e6 in cancer cells. We also compared the accumulation of G-chlorin e6 between normal immortalized esophageal epithelial cells and esophageal cancer cells. Antitumor effects of G-chlorin e6 PDT were finally analyzed in allograft tumor mouse models. RESULTS: PDT in vitro using G-chlorin e6 elicited 9, 000-34,000 times stronger antitumor effects than TS, and there was 70-190 times more G-chlorin e6 accumulated than TS by flow cytometry. G-chlorin e6 accumulated more selectively in esophageal cancer cells than in esophageal immortalized epithelial cells, and in an allograft model, PDT with G-chlorin e6 showed very strong antitumor effects and a 40% complete response (CR) rate. CONCLUSIONS: G-chlorin e6 showed excellent tumor selectivity, and PDT using G-chlorin e6 revealed the strongest anti-tumor effects among all sugar-conjugated chlorins that we have studied. G-chlorin e6 is considered to be the best photosensitizer for next-generation PDT.


Assuntos
Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/patologia , Glucose/administração & dosagem , Fotoquimioterapia/métodos , Porfirinas/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Sinergismo Farmacológico , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Fármacos Fotossensibilizantes/administração & dosagem , Resultado do Tratamento
15.
World Neurosurg ; 109: e715-e723, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29066317

RESUMO

BACKGROUND: Stereotactic radiosurgery (SRS) is generally considered a minimally invasive treatment modality. However, definitive evidence of the efficacy of SRS in the elderly population is still not available. METHODS: The outcomes of 561 elderly and nonelderly patients who underwent SRS for AVM at our institution between 1990 and 2013 were reviewed, analyzed, and compared. Elderly patients were defined as those age ≥60 years at the time of SRS. RESULTS: The elderly cohort comprised 55 patients; the nonelderly cohort, 506. In the elderly cohort, the median age was 65 years, and the duration of follow-up was 91 months. The actuarial obliteration rates were 47% at 3 years, 70% at 4 years, and 76% at 5 years in the elderly cohort, and 57% at 3 years, 76% at 4 years, and 83% at 5 years in the nonelderly cohort. In the elderly cohort, the hemorrhage rates during the post-SRS latent phase were 5.2%/year in patients with hemorrhagic onset and 0%/year in those with nonhemorrhagic onset, and event-free survival (EFS) was 93% at 6 years and 89% at 12 years. The obliteration rate, mortality, and EFS rate were not significantly different between the 2 cohorts, whereas the rate of perifocal edema was significantly lower (P = 0.021) in the elderly cohort. The pre-SRS and post-SRS hemorrhage rates were slightly higher in the elderly cohort, albeit without statistical significance. CONCLUSIONS: Therapeutic effects and outcomes of SRS are similar in elderly and nonelderly patients. Treatment-related neurologic deficits are rare, and longer EFS can be expected.


Assuntos
Fístula Arteriovenosa/cirurgia , Malformações Arteriovenosas Intracranianas/cirurgia , Radiocirurgia/tendências , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Fístula Arteriovenosa/diagnóstico , Fístula Arteriovenosa/mortalidade , Feminino , Seguimentos , Humanos , Malformações Arteriovenosas Intracranianas/diagnóstico , Malformações Arteriovenosas Intracranianas/mortalidade , Masculino , Pessoa de Meia-Idade , Radiocirurgia/mortalidade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
16.
ACS Omega ; 3(8): 9814-9821, 2018 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31459110

RESUMO

A metal- and base-free method is developed for the synthesis of aryl iodides from arylhydrazine hydrochlorides and iodine. A wide variety of aryl iodides can be conveniently synthesized by an equimolar reaction of arylhydrazine hydrochlorides and I2 in dimethyl sulfoxide at 60 °C for 6 h. In the iodination step, arylhydrazines are oxidized by iodine to form arenediazonium salts, which undergo single-electron transfer from iodide anion to give aryl and iodine radicals; subsequent combination of them affords the corresponding aryl iodides.

17.
J Org Chem ; 82(23): 12477-12484, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29094942

RESUMO

Binary systems consisting of benzoyl peroxide (BPO) and diorganyl diselenide are effective in the selective benzoyloxyselenation of internal alkynes to afford the corresponding ß-(benzoyloxy)alkenyl selenides in good yields. In contrast to internal alkynes, terminal alkynes undergo a novel C(sp)-H substitution with the phenylseleno group of the BPO/(PhSe)2 system, providing alkynyl selenides in good yields. Both selenation reactions might proceed via benzoyloxy selenide (PhC(O)O-SeAr) as a key intermediate for electrophilic addition to alkynes. The products alkenyl and alkynyl selenides are expected to be useful synthetic intermediates in organic synthesis.

18.
J Org Chem ; 82(23): 12530-12538, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29092395

RESUMO

A convenient, novel, and metal-free method for the synthesis of 4,4'-diaminotriarylmethanes (DTMs) is described. This process is based on a one-pot condensation of benzylamines with N,N-dimethylaniline derivatives using 4,6-dihydroxysalicylic acid as a co-oxidant and N-iodosuccinimide as an oxidant. To the best of our knowledge, the present method provides the first reported synthesis of DTMs from benzylamines via oxidative C-N bond cleavage and subsequent double C-C bond formations. The obtained DTMs were then easily converted into a series of blue dyes upon treatment with tetrachloro-1,4-benzoquinone (chloranil). Although the production of triarylmethane dyes tends to require the use of toxic heavy metals, the present method is advantageous in that it is a metal-free and straightforward process.

19.
Ann Transl Med ; 5(8): 183, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28616398

RESUMO

Photodynamic therapy (PDT) is a non-invasive antitumor treatment that uses the combination of a photosensitizer, tissue oxygen, and visible light irradiation to produce cytotoxic reactive oxygen species, predominantly singlet oxygen. Currently, first-generation PDT using porfimer sodium with an excimer dye laser, and second-generation PDT using talaporfin sodium PDT with a semiconductor laser are approved by health insurance for use in Japan. However, the cancer cell specificity and selectivity of these treatments are inadequate. Cancer cells consume higher levels of glucose than normal cells and this phenomenon is known as the Warburg effect. Thus, we developed a third-generation PDT, based on the Warburg effect, by synthesizing a novel photosensitizer, sugar-conjugated chlorin, with increased cancer cell-selective accumulation. Glucose-conjugated chlorin (G-chlorin) PDT showed significantly stronger antitumor effects than second-generation talaporfin PDT. We also found that PDT with G-chlorin induced immunogenic cell death which is characterized by the secretion, release, or surface exposure of damage-associated molecular patterns (DAMPs), including calreticulin (CRT) and the high-mobility group box 1 (HMGB1) protein. Mannose-conjugated chlorin (M-chlorin) PDT which targets the mannose receptors on the surface of cancer cells and tumor-associated macrophages (TAMs) in cancer tissue stroma also showed very strong antitumor effects. These novel PDTs using glucose or M-chlorins stand as new candidates for very effective, next-generation PDTs.

20.
J Org Chem ; 82(13): 6647-6655, 2017 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-28616985

RESUMO

A novel synthesis of unsymmetrical aryl sulfides, which requires no transition metal catalyst and no oxidant, was developed. This base-promoted cross-coupling reaction proceeded using arylhydrazines and 1 equiv amount of disulfides under inert gas conditions to afford the unsymmetrical aryl sulfides in good yields.

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