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1.
Bioorg Chem ; 108: 104615, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33484942

RESUMEN

One current approach in the treatment of cancer is the inhibition of cyclin dependent kinase (CDK) enzymes with small molecules. CDK are a class of enzymes, which catalyze the transfer of the terminal phosphate of a molecule of ATP to a protein that acts as a substrate. Among CDK enzymes, CDK2 has been implicated in a variety of cancers, supporting its potential as a novel target for cancer therapy across many tumor types. Here the discovery and development of arylidene-hydrazinyl-thiazole as a potentially CDK2 inhibitors is described, including details of the design and successful synthesis of the series analogs (27a-r) using one-pot approach under eco-friendly ultrasound and microwave conditions. Most of the newly synthesized compounds showed good growth inhibition when assayed for their in-vitro anti-proliferative activity against three cancer cell lines (HepG2, MCF-7 and HCT-116) compared to the reference drug roscovitine, with little toxicity on the normal fibroblast cell lines (WI-38). Furthermore, the compounds exhibiting the highest anti-proliferative activities were tested against a panel of kinase enzymes. These derivatives displayed an outstanding CDK2 inhibitory potential with varying degree of inhibition in the range of IC50 0.35-1.49 µM when compared with the standard inhibitor roscovitine having an IC50 value 0.71 µM. The most promising CDK2 inhibitor (27f) was selected for further studies to determine its effect on the cell cycle progression and apoptosis in HepG2 cell line. The results indicated that this compound implied inhibition in the G2/M phase of the cell cycle, and it is a good apoptotic agent. Finally, Molecular docking study was performed to identify the structural elements which involved in the inhibitory activity with the prospective target, CDK2, and to rationalize the structure-activity relationship (SAR).


Asunto(s)
Antineoplásicos/farmacología , Quinasa 2 Dependiente de la Ciclina/antagonistas & inhibidores , Hidrazinas/farmacología , Hidrocarburos Yodados/farmacología , Simulación del Acoplamiento Molecular , Inhibidores de Proteínas Quinasas/farmacología , Tiazoles/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Quinasa 2 Dependiente de la Ciclina/metabolismo , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Hidrazinas/química , Hidrocarburos Yodados/química , Estructura Molecular , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Relación Estructura-Actividad , Tiazoles/química , Células Tumorales Cultivadas
2.
Environ Mol Mutagen ; 62(3): 168-176, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33484035

RESUMEN

Drinking water disinfection by-products (DBPs), including the ubiquitous trihalomethanes (THMs), are formed during the treatment of water with disinfectants (e.g., chlorine, chloramines) to produce and distribute potable water. Brominated THMs (Br-THMs) are activated to mutagens via glutathione S-transferase theta 1 (GSTT1); however, iodinated THMs (I-THMs) have never been evaluated for activation by GSTT1. Among the I-THMs, only triiodomethane (iodoform) has been tested previously for mutagenicity in Salmonella and was positive (in the absence of GSTT1) in three strains (TA98, TA100, and BA13), all of which have error-prone DNA repair (pKM101). We evaluated five I-THMs (chlorodiiodomethane, dichloroiodomethane, dibromoiodomethane, bromochloroiodomethane, and triiodomethane) for mutagenicity in Salmonella strain RSJ100, which expresses GSTT1, and its homologue TPT100, which does not; neither strain has pKM101. We also evaluated chlorodiiodo-, dichloroiodo-, and dibromoiodo-methanes in strain TA100 +/- rat liver S9 mix; TA100 has pKM101. None was mutagenic in any of the strains. The I-THMs were generally more cytotoxic than their brominated and chlorinated analogues but less cytotoxic than analogous trihalonitromethanes tested previously. All five I-THMs showed similar thresholds for cytotoxicity at ~2.5 µmoles/plate, possibly due to release of iodine, a well-known antimicrobial. Although none of these I-THMs was activated by GSTT1, iodoform appears to be the only I-THM that is mutagenic in Salmonella, only in strains deficient in nucleotide excision repair (uvrB) and having pKM101. Given that only iodoform is mutagenic among the I-THMs and is generally present at low concentrations in drinking water, the I-THMs likely play little role in the mutagenicity of drinking water.


Asunto(s)
Agua Potable/química , Mutagénesis/efectos de los fármacos , Salmonella/efectos de los fármacos , Trihalometanos/toxicidad , Animales , Cloraminas/efectos adversos , Cloraminas/farmacología , Clorofluorocarburos de Metano/efectos adversos , Clorofluorocarburos de Metano/farmacología , Desinfectantes/efectos adversos , Desinfectantes/farmacología , Glutatión Transferasa/química , Humanos , Hidrocarburos Yodados/efectos adversos , Hidrocarburos Yodados/farmacología , Mutágenos/toxicidad , Ratas , Salmonella/genética , Trihalometanos/farmacología
3.
Future Med Chem ; 12(13): 1205-1211, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32515228

RESUMEN

Background: Resistance developments against established antibiotics are an emerging problem for antibacterial therapies. Novel antibiotics are urgently needed. Materials & methods: We developed novel small-molecule antibacterials which are easily accessible in a simple one-pot synthesis. The central cyclopentaindole core is substituted with two indole residues. Various indole and cyclopentane substituents have been introduced. Additionally, first indole substituted propene compounds as ring-open variants of the cyclopentaindoles have been yielded and evaluated as antibacterials against Staphylococcus aureus and Enterococcus strains. Results: Most effective compounds have been those with a bromo cyclopentane and a chloro indole substitution. First lead compounds were identified with promising activities similar to that observed in vitro for last resort antibiotics, so that the novel compounds enriche the pool of perspective small-molecule antibacterial drug candidates.


Asunto(s)
Antibacterianos/farmacología , Enterococcus/efectos de los fármacos , Hidrocarburos Bromados/farmacología , Hidrocarburos Yodados/farmacología , Bibliotecas de Moléculas Pequeñas/farmacología , Staphylococcus/efectos de los fármacos , Antibacterianos/síntesis química , Antibacterianos/química , Hidrocarburos Bromados/síntesis química , Hidrocarburos Bromados/química , Hidrocarburos Yodados/síntesis química , Hidrocarburos Yodados/química , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Bibliotecas de Moléculas Pequeñas/síntesis química , Bibliotecas de Moléculas Pequeñas/química
4.
Nanoscale ; 12(20): 11008-11025, 2020 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-32301458

RESUMEN

Photodynamic therapy (PDT), as one of the most powerful photo-therapeutic strategies for cancer treatment with minimum invasiveness, can effectively damage local tumor cells and significantly induce systemic antitumor immunity. However, current nanotechnology-assisted PDT-immunomodulators have either poor penetration for deep tumors or low singlet oxygen generation. Herein, we construct a novel theranostic nanocarrier (HA-PEG-CyI, HPC) by inducing the self-assembly of PEGylated CyI and attaching the ligand HA to its surface. The prepared HPC can be used as an ideal PDT-immunomodulator for synergistic cancer therapy. CyI is an iodinated-cyanine dye with enhanced singlet oxygen generation ability as well as excellent photo-to-photothermal and near-infrared fluorescence imaging properties. Under 808 nm laser irradiation, the prepared HPC can generate both reactive oxygen species (ROS) and elevate temperature which can subsequently result in apoptosis and necrosis at tumor sites. Moreover, the HPC-induced cell death can generate a series of acute inflammatory reactions, leading to systemic immunity induction and secondary death of tumor cells, which further results in reducing tumor recurrence. In vitro and in vivo results show that HPC can enhance the tumor targeting efficacy, generate ROS efficiently and exhibit a high temperature response under NIR irradiation, which working together can activate immune responses for synergistic phototherapy on tumor cells. Accordingly, the proposed multi-functional HPC nanocarriers represent an important advance in PDT and can be used as a superior cancer treatment strategy with great promise for clinical applications.


Asunto(s)
Carbocianinas , Portadores de Fármacos , Hidrocarburos Yodados , Factores Inmunológicos , Nanoestructuras , Neoplasias Experimentales , Fotoquimioterapia , Animales , Apoptosis/efectos de los fármacos , Carbocianinas/química , Carbocianinas/farmacocinética , Carbocianinas/farmacología , Línea Celular Tumoral , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacología , Femenino , Humanos , Hidrocarburos Yodados/química , Hidrocarburos Yodados/farmacocinética , Hidrocarburos Yodados/farmacología , Factores Inmunológicos/química , Factores Inmunológicos/farmacocinética , Factores Inmunológicos/farmacología , Ratones , Ratones Endogámicos BALB C , Nanoestructuras/química , Nanoestructuras/uso terapéutico , Neoplasias Experimentales/diagnóstico por imagen , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/metabolismo , Células RAW 264.7
5.
Arch Oral Biol ; 105: 65-71, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31276940

RESUMEN

OBJECTIVES: The aim of this in vitro study was to evaluate the effectiveness of an iodoform paste and silver-coated abutments in preventing the microbial colonization and leakage through the implant-abutment interface of morse taper and internal hexagon implants. MATERIAL AND METHODS: Seventy-two implants with morse taper (n = 36) or internal hexagon connections (n = 36) were investigated. Implants were treated with iodoform paste (n = 12), silver-coated abutments (n = 12), or control (n = 12). After saliva incubation, Checkerboard DNA-DNA hybridization was used to identify and quantify up to 43 microbial species colonizing the inner parts of the implants. ANOVA-Type and Wald-Type analyses of variance were used to investigate the relative effects and their interaction. Friedman- Conover test adjusted by Benjamini-Hockberg FDR were performed for pairwise multiple comparisons. Significance was set as p < 0.05. RESULTS: Analyses of variance indicate a significant interaction between connections, antimicrobial treatments, and species. The frequency of contamination was reduced in the implants submitted to the antimicrobial treatments. Iodoform and silver-coated abutments significantly reduced the total microbial counts in the internal hexagon implants. The lower microbial counts were recorded for morse taper implants with silver-coated abutments. CONCLUSIONS: Iodoform paste and silver-coated abutments have influenced the microbial leakage through the implant-abutment interface, by reducing both frequency of contamination and microbial levels. Treatments were not effective in reducing the counts of the target species.


Asunto(s)
Pilares Dentales/microbiología , Implantes Dentales/microbiología , Hidrocarburos Yodados/farmacología , Plata/farmacología , Antibacterianos/farmacología , Bacterias/aislamiento & purificación , Diseño de Implante Dental-Pilar , Técnicas In Vitro , Hibridación de Ácido Nucleico
6.
ACS Appl Mater Interfaces ; 11(29): 25720-25729, 2019 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-31246000

RESUMEN

Phototheranostics, which combines deep tissue imaging and phototherapy [photodynamic therapy (PDT) and/or photothermal therapy (PTT)] via light irradiation, is a promising strategy to treat tumors. Near-infrared (NIR) cyanine dyes are researched as potential phototheranostics reagents for their excellent photophysical properties. However, the low singlet oxygen generation efficiency of cyanine dyes often leads to inadequate therapeutic efficacy for tumors. Herein, we modified an indocyanine green derivative Cy7 with heavy atom iodine to form a novel NIR dye CyI to improve the reactive oxygen species (ROS) production and heat generation while, at the same time, maintain their fluorescence characteristics for in vivo noninvasive imaging. More importantly, in vitro and in vivo therapeutic results illustrated that CyI could quickly and simultaneously generate enhanced ROS and heat to induce more cancer cell apoptosis and higher inhibition rates in deep HepG2 tumors than other noniodinated NIR dyes upon NIR irradiation. Besides, low toxicity of the resulted iodinated NIR dyes was confirmed by in vivo biodistribution and acute toxicity. Results indicate that this low toxic NIR dye could be an ideal phototheranostics agent for deep tumor treatments. Our study presents a novel approach to achieve the fast-synergistic PDT/PTT treatment in deep tissues.


Asunto(s)
Carbocianinas , Hidrocarburos Yodados , Hipertermia Inducida , Neoplasias Experimentales , Fototerapia , Animales , Carbocianinas/química , Carbocianinas/farmacocinética , Carbocianinas/farmacología , Células Hep G2 , Humanos , Hidrocarburos Yodados/química , Hidrocarburos Yodados/farmacocinética , Hidrocarburos Yodados/farmacología , Ratones , Ratones Desnudos , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Neoplasias Experimentales/terapia , Especies Reactivas de Oxígeno/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
7.
Molecules ; 24(5)2019 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-30823489

RESUMEN

In this work, several benzothiazole-based aminosquaraine dyes, displaying strong absorption within the so-called phototherapeutic window (650⁻800 nm), were synthesized. The ability, of all the new dyes, to generate singlet oxygen was assessed by determining the correspondent phosphorescence emission and through the comparison with a standard. The quantum yields of singlet oxygen generation were determined and exhibited to be strongly dependent on the nature of the amino substituents introduced in the squaric ring. The photodynamic activity of the synthesized dyes was tested against four human tumor cell lines: breast (MCF-7), lung (NCI-H460), cervical (HeLa) and hepatocellular (HepG2) carcinomas; and a non-tumor porcine liver primary cell culture (PLP2). All the compounds synthesized were found to be able to inhibit tumor cells growth upon irradiation more than in the dark, in most of the cases, very significantly. Considering the photodynamic activity exhibited and the low toxicity displayed for the non-tumor cells, some of the synthetized dyes can be regarded as potential candidates as photosensitizers for PDT.


Asunto(s)
Ciclobutanos , Citotoxinas , Hidrocarburos Yodados , Neoplasias/tratamiento farmacológico , Fotoquimioterapia , Fármacos Fotosensibilizantes , Animales , Ciclobutanos/síntesis química , Ciclobutanos/química , Ciclobutanos/farmacología , Citotoxinas/síntesis química , Citotoxinas/química , Citotoxinas/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Células HeLa , Células Hep G2 , Humanos , Hidrocarburos Yodados/síntesis química , Hidrocarburos Yodados/química , Hidrocarburos Yodados/farmacología , Células MCF-7 , Neoplasias/metabolismo , Neoplasias/patología , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Porcinos
8.
Med Sci Monit ; 24: 9063-9072, 2018 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-30547901

RESUMEN

BACKGROUND This study was conducted to observe the influence of different time intervals between prior cervical conization and posterior hysterectomy on postoperative infection in female patients with cervical intraepithelial neoplasia or cancer. MATERIAL AND METHODS Medical records of 170 patients who underwent hysterectomy following cervical conization between November 2010 and September 2016 at the Zhenjiang 4th Hospital were reviewed. According to the interval between hysterectomy and cervical conization, patients were classified into 1-2-week, 4-5-week, and 6-week groups. The outcomes of 46 patients who underwent conization with iodoform gauze inside the vagina were observed. RESULTS The total postoperative infection rate after hysterectomy was 25.3% (43/170). The expression levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and high mobility group box 1 (HMGB1) in the cervical secretions and tissues were found to gradually increase, peaking at 2 weeks after conization, then significantly decreasing 3-6 weeks onwards. Compared with the 1-2-week group, the 4-5-week and 6-week groups exhibited significantly lower infection rates (2/42, 4.8%, 4-5-week group; 0%, 0/33, 6-week group; vs. 41/95, 43.2%, 1-2-week group; p<0.001). In the 1-2-week group in particular, the postoperative infection rate after laparoscopic hysterectomy was significantly higher than the rate after abdominal hysterectomy (21/35, 60% vs. 20/60, 33%, p=0.0177). In addition, the vaginal and cervical wound infection rates after conization in patients treated with iodoform were significantly lower than the rates in those without iodoform treatment (p<0.05). CONCLUSIONS Hysterectomy should be performed at least 4 weeks after conization. Treatment with iodoform would be beneficial.


Asunto(s)
Cuello del Útero/cirugía , Infección de la Herida Quirúrgica/etiología , Adulto , Cuello del Útero/citología , China , Conización/métodos , Femenino , Proteína HMGB1/análisis , Hospitales , Humanos , Hidrocarburos Yodados/farmacología , Histerectomía/métodos , Interleucina-6/análisis , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Periodo Posoperatorio , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/análisis , Neoplasias del Cuello Uterino/cirugía , Vagina/cirugía , Displasia del Cuello del Útero/cirugía
9.
J Contemp Dent Pract ; 19(6): 680-683, 2018 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-29959296

RESUMEN

AIM: The study aimed to evaluate the efficacy of root canal sealer's antimicrobial activity against Enterococcus faecalis. MATERIALS AND METHODS: Root canal sealers with the brands Endoflas FS, AH Plus, and Tubli-Seal EWT were selected. Enterococcus faecalis organisms' zone of inhibition was measured. Tukey post hoc tests and one-way analysis of variance (ANOVA) were used to compare the data among study groups and within its group. The data were said to be statistically significant with an established p-value less than 0.05. RESULTS: The maximum zone of inhibition (23.20 ± 1.202 mm) was shown by Endoflas FS sealer; AH Plus and Tubli-Seal showed the inhibition zone of (18.42 ± 1.023) and (16.88 ± 0.962) respectively, following Endoflas FS. The ANOVA test showed p < 0.0001, which is highly statistically significant. AH Plus and Endoflas FS showed a statistically significant difference of 0.04 and 0.001 in between groups, and there was no statistically significant difference in the Tubli-Seal group from Tukey post hoc test. CONCLUSION: The study showed that Endoflas FS sealer has a significant antimicrobial effect against E. faecalis. CLINICAL SIGNIFICANCE: In clinical situation, despite perfect che-momechanical root canal preparation, persistence of microorganisms may reinfect the root canal. Therefore, endodontic root canal sealers play a major role in the eradication of bacteria. The polymicrobial nature of endodontic infection plays a main role during the usage of endodontic sealer with antimicrobial agents, which in turn reduces the failure of endodontic treatment.


Asunto(s)
Antiinfecciosos/farmacología , Sulfato de Bario/farmacología , Enterococcus faecalis/efectos de los fármacos , Resinas Epoxi/farmacología , Hidrocarburos Yodados/farmacología , Materiales de Obturación del Conducto Radicular/farmacología , Cemento de Óxido de Zinc-Eugenol/farmacología , Combinación de Medicamentos , Pruebas de Sensibilidad Microbiana
10.
Biomed Res Int ; 2018: 8198795, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29619378

RESUMEN

BACKGROUND: The study aim is to avoid tooth extraction by nonsurgical treatment of periapical lesion. It assesses healing progress in response to calcium hydroxide-iodoform-silicon oil paste (CHISP). Numeric Pain Rating Scale was used to validate the approach. Furthermore, CHISP was used to treat cystic lesions secondary to posttraumatic avulsion of permanent teeth. MATERIALS AND METHODS: Over 200 patients with radicular cysts were treated with CHISP through the root canal. Radiographs were used to verify lesion size and position, ensure correct delivery to the site, and monitor the progress of bone healing in the lesion area. Ten males and 10 females were randomly selected for statistical assessment. RESULTS: No severe pain, complications, or failure in cyst healing was reported. Complete healing was achieved in an average of 75 days. Furthermore, healing of radicular cyst secondary to posttraumatic tooth avulsion was successful. CONCLUSION: CHISP indicated an antiseptic effect, which enhanced and shortened healing time of periapical lesions. The less invasive procedure avoids tooth extraction and reduces bone resorption. Cyst management with CHISP can remedy failed root canal treatments. The results show a bone regenerative capacity of CHISP suggested in first rapid phase and a second slow phase.


Asunto(s)
Hidróxido de Calcio/uso terapéutico , Hidrocarburos Yodados/uso terapéutico , Quiste Radicular/tratamiento farmacológico , Silicio/uso terapéutico , Hidróxido de Calcio/efectos adversos , Hidróxido de Calcio/farmacología , Femenino , Humanos , Hidrocarburos Yodados/efectos adversos , Hidrocarburos Yodados/farmacología , Masculino , Dolor/etiología , Silicio/efectos adversos , Silicio/farmacología , Cicatrización de Heridas/efectos de los fármacos
11.
J Microencapsul ; 35(1): 49-61, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29308689

RESUMEN

OBJECTIVES: Curcumin (Cur) exhibits weak microbicidal activity owing to high lipophilicity and low cell permeability. Therefore, in the present investigation, Cur was iodinated using elemental iodine (I2) to synthesise Cur-I2 powder that was later formulated as Cur-I2 dermal cream and characterised in vitro for antimicrobial and antioxidant activities. METHODS AND RESULTS: Electrophilic addition of I2 saturated the olefinic bonds of Cur, as confirmed by UV/visible spectroscopy, FT-IR, 1H NMR and DSC techniques. In addition, in vitro skin permeation and retention analysis indicated that Cur-I2 cream followed the first order and Higuchi model for drug release through the rat skin. The minimum inhibitory concentration (MIC) of Cur-I2 powder was measured to be 60 and 90 µg/ml significantly (p < 0.05) lower than 150 and 120 µg/ml of Cur against Staphylococcus aureus and Escherichia coli, respectively. Moreover, Cur-I2 also exhibited strong antioxidant potential. CONCLUSIONS: Cur-I2 cream warrants further in vivo study to scale up the technology for clinical translation.


Asunto(s)
Antiinfecciosos , Antioxidantes , Curcumina , Escherichia coli/crecimiento & desarrollo , Hidrocarburos Yodados , Crema para la Piel , Staphylococcus aureus/crecimiento & desarrollo , Antiinfecciosos/química , Antiinfecciosos/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Curcumina/química , Curcumina/farmacología , Hidrocarburos Yodados/química , Hidrocarburos Yodados/farmacología , Crema para la Piel/química , Crema para la Piel/farmacología
12.
J Clin Pediatr Dent ; 41(6): 450-455, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28937906

RESUMEN

OBJECTIVES: An association between root canal sealers and periapical lesions in primary dentition has been suggested, yet the chemical-protein interactions that may be involved in it have not been studied. The present study explored root sealer components' effect on periapical tissue proteins using bioinformatics tools. STUDY DESIGN: For each chemical component of Endoflas F.S. root sealing material we identified the known and predicted target proteins, using STITCH (search tool for interactions of chemicals http://stitch.embl.de/ ). Identified target proteins were grouped into functional categories using the annotation clustering tool from DAVID, the Database for Annotation, Visualization and Integrated Discovery ( http://david.abcc.ncifcrf.gov/ ). STRING Protein-Protein Interaction network database identified associations between the proteins. RESULTS: Sixteen proteins identified with STITCH served as input to DAVID annotation clustering tool. Only ZnO and Eugenol targeted proteins had statistically significant annotations. Gene Ontology terms of ZnO and Eugenol targeted proteins demonstrated that these proteins respond to mechanical stimulus and to oxidative stress. They highlight these proteins' role in the positive regulation of transcription, gene expression, cell proliferation and apoptosis, and their complementary role in the negative regulation of cell death. CONCLUSION: When stimulated by Zinc Oxide, Eugenol and Calcium hydroxide, chemical-protein and subsequent protein-protein interactions result in cell proliferation in the periapical area. Our findings indicate that certain root sealers components may cause enlargement of the permanent tooth follicle. Dentists should be aware of this phenomenon and radiographically monitor root canal treated teeth until shedding.


Asunto(s)
Sulfato de Bario/farmacología , Hidrocarburos Yodados/farmacología , Tejido Periapical/efectos de los fármacos , Proteínas/efectos de los fármacos , Proteínas/fisiología , Cemento de Óxido de Zinc-Eugenol/farmacología , Combinación de Medicamentos
13.
Pediatr Dent ; 39(2): 145-149, 2017 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-28390465

RESUMEN

PURPOSE: The purpose of this study was to evaluate the effect of five endodontic materials for primary teeth on in vitro mixed-species biofilms. METHODS: Zinc oxide eugenol (ZOE) cement, Vitapex, Calen paste thickened with zinc oxide (ZO), pure calcium hydroxide (Ca(OH)2) paste, and iodoform were evaluated. Sterile water was used as a control. Mixed-species biofilm was incubated in anaerobic conditions for 21 days. The biofilm specimens were placed in contact with the endodontic materials for periods of seven and 30 days. The biofilm was studied by using confocal laser scanning microscopy. The cell viability ratio was calculated. The results were analyzed using analysis of variance and Tukey tests. RESULTS: There was a statistically significant difference between groups at both seven and 30 days (F equals 73,073, P=0.00). After 30 days, 69 percent, 51 percent, and 35 percent of the biofilm volume fluoresced red, indicating the proportion of bacteria killed by iodoform, Vitapex, and ZOE cement, respectively. Calen plus ZO and pure Ca(OH)2 paste were the least effective materials against the biofilms. CONCLUSIONS: Pure iodoform paste and iodoform containing Vitapex were the most effective materials against the biofilms. Vitapex appears to be a suitable endodontic material for primary teeth.


Asunto(s)
Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Materiales de Obturación del Conducto Radicular/farmacología , Diente Primario/microbiología , Hidróxido de Calcio/farmacología , Humanos , Hidrocarburos Yodados/farmacología , Técnicas In Vitro , Ensayo de Materiales , Microscopía Confocal , Siliconas/farmacología , Diente Primario/diagnóstico por imagen , Óxido de Zinc , Cemento de Óxido de Zinc-Eugenol/farmacología
14.
Bioorg Med Chem Lett ; 26(8): 1889-93, 2016 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-26988304

RESUMEN

We report the pharmacophore of the peroxisome proliferator-activated receptor δ (PPARδ) agonist natural product phosphoiodyn A is the phosphonate core. Synthesis of simplified phosphonate esters 13 and 15 provide structurally novel, highly selective and potent PPARδ agonists (EC50=78 and 112 nM, respectively). Further, both compounds demonstrate significant neuroprotective activity in an in vitro cellular model indicating that phosphonates may be an effective novel scaffold for the design of therapeutics for the treatment of neurodegenerative disorders.


Asunto(s)
Hidrocarburos Yodados/farmacología , Enfermedades Neurodegenerativas/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Compuestos Organofosforados/farmacología , PPAR delta/agonistas , PPAR-beta/agonistas , Poliinos/farmacología , Relación Dosis-Respuesta a Droga , Humanos , Hidrocarburos Yodados/síntesis química , Hidrocarburos Yodados/química , Estructura Molecular , Fármacos Neuroprotectores/síntesis química , Fármacos Neuroprotectores/química , Compuestos Organofosforados/síntesis química , Compuestos Organofosforados/química , Poliinos/síntesis química , Poliinos/química , Relación Estructura-Actividad
15.
Int Endod J ; 49(8): 737-45, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26174479

RESUMEN

AIM: To evaluate the cytotoxicity, oxidative stress and genotoxicity in vitro of four iodoform pastes and three calcium hydroxide pastes. METHODOLOGY: Peripheral blood mononuclear cells (PBMCs) and pure calf thymus DNA (dsDNA) were exposed to extracts of the pastes. Cytotoxicity was assessed with the MTT assay. Generation of reactive oxygen species (ROS) was evaluated using a DCFH-DA assay, and lipid peroxidation was evaluated using a TBARS assay. Genotoxicity was evaluated using the alkaline comet assay and Genomodifier capacity assay (GEMO). All tests were performed after 24 h and 72 h of cell exposure, except GEMO. After performing the Kolmogorov-Smirnov test, data were analysed by Kruskal-Wallis and Dunn's post-tests, and anova with Dunnett's post-test, with a significance level established at P < 0.05. RESULTS: The MTT assay revealed that chlorhexidine, Maxitrol and neomycin sulphate + bacitracin pastes decreased cell viability after 24 h (P < 0.05). No group was associated with a significant decreased cell viability or lipid peroxidation after 72 h. Calcium hydroxide pastes increased the cell viability levels at both experimental times (P < 0.05). Lipid peroxidation was observed with the exposure of cells to calcium hydroxide pastes after 24 h (P < 0.05). Exposure to chlorhexidine, Guedes-Pinto and calcium hydroxide pastes resulted in a significant increase in ROS after 24 h (P < 0.05), whereas iodoform pastes and Calen thickened with zinc oxide significantly increased the ROS after 72 h (P < 0.05). The comet assay revealed that exposure of the PBMCs to iodoform pastes did not damage DNA at either period of time (P > 0.05). However, chlorhexidine paste caused DNA damage in dsDNA (P < 0.05). Calcium hydroxide pastes caused DNA damage in both tests (P < 0.05). CONCLUSION: The pastes varied in their ability to induce cytotoxicity, genotoxicity and oxidative stress. In general, Guedes-Pinto, Maxitrol and neomycin sulphate + bacitracin pastes exhibited better biocompatibility in vitro.


Asunto(s)
ADN/efectos de los fármacos , Hidrocarburos Yodados/farmacología , Leucocitos Mononucleares/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Materiales de Obturación del Conducto Radicular/farmacología , Análisis de Varianza , Animales , Bovinos , Daño del ADN , Humanos , Leucocitos Mononucleares/metabolismo , Ensayo de Materiales , Especies Reactivas de Oxígeno/metabolismo , Estadísticas no Paramétricas , Diente Primario , Pruebas de Toxicidad
16.
J Environ Health ; 78(2): 14-9, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26502561

RESUMEN

Fumigation techniques such as chlorine dioxide, vaporous hydrogen peroxide, and paraformaldehyde previously used to decontaminate items, rooms, and buildings following contamination with Bacillus anthracis spores are often incompatible with materials (e.g., porous surfaces, organics, and metals), causing damage or residue. Alternative fumigation with methyl bromide is subject to U.S. and international restrictions due to its ozone-depleting properties. Methyl iodide, however, does not pose a risk to the ozone layer and has previously been demonstrated as a fumigant for fungi, insects, and nematodes. Until now, methyl iodide has not been evaluated against Bacillus anthracis. Sterne strain Bacillus anthracis spores were subjected to methyl iodide fumigation at room temperature and at 550C. Efficacy was measured on a log-scale with a 6-log reduction in CFUs being considered successful compared to the U.S. Environmental Protection Agency biocide standard. Such efficacies were obtained after just one hour at 55 °C and after 12 hours at room temperature. No detrimental effects were observed on glassware, PTFE O-rings, or stainless steel. This is the first reported efficacy of methyl iodide in the reduction of Bacillus anthracis spore contamination at ambient and elevated temperatures.


Asunto(s)
Antibacterianos/farmacología , Bacillus anthracis/efectos de los fármacos , Fumigación/métodos , Hidrocarburos Yodados/farmacología , Esporas Bacterianas/efectos de los fármacos , Temperatura
17.
Org Lett ; 17(22): 5544-6, 2015 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-26509219

RESUMEN

The convergent total synthesis of the marine natural product phosphoiodyn A, a nanomolar agonist of human peroxisome proliferator-activated receptor delta (hPPARδ), was achieved in five steps total from commercially available and inexpensive starting materials. The synthesis relies on the unprecedented regioselective hydrozirconation of a terminal acetylene in the presence of a conjugated 1,3-diyne and on ammonolysis of a ß-chlorophosphonic acid monoester. The scheme also provides the newly isolated placotylene A, an inhibitor of bone marrow-derived macrophage (BMM) differentiation.


Asunto(s)
Diinos/síntesis química , Alcoholes Grasos/síntesis química , Hidrocarburos Yodados/síntesis química , Compuestos Organofosforados/síntesis química , Poliinos/síntesis química , Acetileno/química , Diferenciación Celular , Diinos/química , Diinos/farmacología , Alcoholes Grasos/química , Alcoholes Grasos/farmacología , Humanos , Hidrocarburos Yodados/química , Hidrocarburos Yodados/farmacología , Macrófagos/efectos de los fármacos , Estructura Molecular , Compuestos Organofosforados/química , Compuestos Organofosforados/farmacología , PPAR delta/agonistas , Poliinos/química , Poliinos/farmacología
18.
Steroids ; 98: 153-65, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25732071

RESUMEN

The regioselective Cu(I)-catalyzed 1,3-dipolar cycloaddition of 3-methoxyestrane 17α- and 17ß-azide epimers (3 and 5) with different terminal alkynes afforded novel 1,4-substituted triazolyl derivatives (8a-f and 11a-f). If the Ph3P in the classical CuAAC process was replaced by Et3N, the formation of small quantities of 5-iodotriazoles (9a-f and 11a-f) was observed. For the preparation of 5-iodo-1,2,3-triazoles (9a-f and 11a-f), an improved method was developed, directly from steroidal azides and terminal alkynes, in reactions mediated by CuI and ICl as iodinating agents. The antiproliferative activities of the structurally related triazoles were determined in vitro with the microculture tetrazolium assay on six malignant human cell lines of gynecological origin (HeLa, A2780, MCF7, MDA-MB-231, MDA-MB-361 and T47D). X-ray analysis revealed the presence of the iodo substituent on the 1,2,3-triazole ring.


Asunto(s)
Antineoplásicos , Cobre/química , Citotoxinas , Estranos , Hidrocarburos Yodados , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Catálisis , Citotoxinas/síntesis química , Citotoxinas/química , Citotoxinas/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Estranos/síntesis química , Estranos/química , Estranos/farmacología , Células HeLa , Humanos , Hidrocarburos Yodados/síntesis química , Hidrocarburos Yodados/química , Hidrocarburos Yodados/farmacología , Células MCF-7
19.
Appl Microbiol Biotechnol ; 99(7): 3327-37, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25661813

RESUMEN

Response surface methodology (RSM) was used to optimize the production of volatile fatty acids (VFAs) and hydrogen from mixed anaerobic cultures of Saccharina japonica with respect to two independent variables: methanogenic inhibitor concentration and temperature. The effects of four methanogenic inhibitors on acidogenic processes were tested, and qualitative microbial analyses were carried out. Escherichia, Acinetobacter, and Clostridium were the most predominant genera in samples treated with chloroform (CHCl3), iodoform (CHI3), 2-bromoethanesulfonate (BES), or ß-cyclodextrin (ß-CD), respectively. RSM showed that the production of VFAs reached a peak of 12.5 g/L at 38.6 °C in the presence of 7.4 g/L ß-CD; these were the conditions under which hydrogen production was also nearly maximal. The quantitative polymerase chain reaction (qPCR) showed that shifts in the bacterial community population correlated with the concentrations of ß-CD indicating that this compound effectively inhibited methanogens.


Asunto(s)
Biotecnología/métodos , Ácidos Grasos Volátiles/biosíntesis , Hidrógeno/metabolismo , Consorcios Microbianos , Phaeophyceae/metabolismo , Ácidos Alcanesulfónicos/farmacología , Anaerobiosis , Biotecnología/instrumentación , Cloroformo/farmacología , Hidrocarburos Yodados/farmacología , Metano/metabolismo , Consorcios Microbianos/efectos de los fármacos , Consorcios Microbianos/genética , Phaeophyceae/citología , Phaeophyceae/efectos de los fármacos , ARN Ribosómico 16S , Temperatura , beta-Ciclodextrinas/farmacología
20.
Stomatologiia (Mosk) ; 93(2): 10-3, 2014.
Artículo en Ruso | MEDLINE | ID: mdl-24781120

RESUMEN

The aim of the current study was to assess antibacterial and cytotoxic properties of Biodentine (Septodont), Rootdent (TehnoDent) and adhesive Futurabond НР (Voco). Two lines of experiments were carried out using cements water solutions and firm tablet-like samples (made by means of special pattern). Citotoxic activity was tested on NCTC L929 mice line fibroblasts culture. All the examined materials showed antibacterial activity against E. coli, S. aureus, C. albiсans, St. faecalis, mostly evident in Futurabond and the poorest in Biodentine samples. As for cytotoxic properties, Biodentine proved not to suppress metabolic activity stimulating odontotropic impact. The results confirm the analyzed materials to be a useful tool for deep caries lesions and initial pulpitis treatment.


Asunto(s)
Antiinfecciosos/farmacología , Creosota/farmacología , Pulpa Dental/microbiología , Hidrocarburos Yodados/farmacología , Metacrilatos/farmacología , Pulpitis/microbiología , Timol/farmacología , Animales , Candida albicans/efectos de los fármacos , Línea Celular , Creosota/efectos adversos , Daño del ADN , Caries Dental/microbiología , Pulpa Dental/irrigación sanguínea , Combinación de Medicamentos , Enterococcus faecalis/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Fibroblastos/microbiología , Hidrocarburos Yodados/efectos adversos , Hiperemia/microbiología , Metacrilatos/efectos adversos , Ratones , Staphylococcus aureus/efectos de los fármacos , Timol/efectos adversos
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