Tag: M.W=350-400

Costa, David published the artcileSinglet oxygen scavenging activity of non-steroidal anti-inflammatory drugs, Product Details of C20H17FO4S, the publication is Redox Report (2008), 13(4), 153-160, database is CAplus and MEDLINE.

It has long been known that singlet oxygen (¹O₂) is generated during inflammatory processes. Once formed in substantial amounts, ¹O₂ may have an important role in mediating the destruction of infectious agents during host defense. On the other hand, ¹O₂ is capable of damaging almost all biol. mols. and is particularly genotoxic, which gives a special relevance to the scavenging of this ROS throughout anti-inflammatory treatments. Considering that the use of non-steroidal anti-inflammatory drugs (NSAIDs) constitutes a first approach in the treatment of persistent inflammatory processes (due to their ability to inhibit cyclooxygenase), a putative scavenging activity of NSAIDs for ¹O₂ would also represent a significant component of their therapeutic effect. The aim of the present study was to evaluate the scavenging activity for ¹O₂ by several chem. families of NSAIDs. The results suggested that the pyrazole derivatives (dipyrone and aminopyrine) are, by far, the most potent scavengers of ¹O₂ (much more potent compared to the other tested NSAIDs), displaying IC₅₀-values in the low micromolar range. There was a lack of activity for most of the arylpropionic acid derivatives tested, with only naproxen and indoprofen displaying residual activities, as for the oxazole derivative, oxaprozin. On the other hand, the pyrrole derivatives (tolmetin and ketorolac), the indolacetic acid derivatives (indomethacin, and etodolac), as well as sulindac and its metabolites (sulindac sulfide and sulindac sulfone) displayed scavenging activity in the high micromolar range. Thus, the scavenging effect observed for dipyrone and aminopyrine will almost certainly contribute to their healing effect in the treatment of prolonged or chronic inflammation, while that of the other studied NSAIDs may have a lower contribution, though these assumptions still require further in vivo validation.

Redox Report published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C20H17FO4S, Product Details of C20H17FO4S.

Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem

Costa, David published the artcileHydrogen peroxide scavenging activity by non-steroidal anti-inflammatory drugs, Quality Control of 59973-80-7, the publication is Life Sciences (2005), 76(24), 2841-2848, database is CAplus and MEDLINE.

Hydrogen peroxide (H₂O₂) was shown to be formed during inflammatory processes and is implicated in its pathophysiol. Thus, a putative scavenging activity against this reactive oxygen specie (ROS) by anti-inflammatory drugs may be of great therapeutical value. The present study was undertaken to evaluate the scavenging activity for H₂O₂ by several non-steroidal anti-inflammatory drugs (NSAIDs), namely indomethacin, acemetacin, etodolac, tolmetin, ketorolac, oxaprozin, sulindac, and its metabolites sulindac sulfide and sulindac sulfone. The H₂O₂ scavenging assay was performed by measuring H₂O₂-elicited lucigenin chemiluminescence using a microplate reader. The specificity of the method was confirmed by the use of catalase, which completely prevented the H₂O₂-induced lucigenin chemiluminescence. The endogenous antioxidants melatonin and reduced glutathione (GSH) were used as pos. controls. The obtained results demonstrated that all the studied NSAIDs display H₂O₂ scavenging activity, although in different extents. The ranking order of potency found was sulindac sulfone > sulindac sulfide > GSH > sulindac > indomethacin > acemetacin > etodolac > oxaprozin > ketorolac â‰?melatonin > tolmetin.

Life Sciences published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C20H17FO4S, Quality Control of 59973-80-7.

Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem

Witta, Samir E. published the artcileA phase I and pharmacokinetic study of exisulind and docetaxel in patients with advanced solid tumors, SDS of cas: 59973-80-7, the publication is Clinical Cancer Research (2004), 10(21), 7229-7237, database is CAplus and MEDLINE.

Exisulind (sulindac sulfone, FGN-1, Aptosyn) is a sulindac metabolite that induces apoptosis via inhibition of cyclic GMP-phosphodiesterase. This agent demonstrated tumor growth inhibition in rodent models of colon, breast, prostate, and lung carcinogenesis. In an orthotopic model of human non-small-cell lung cancer, the combination of exisulind and docetaxel prolonged survival in athymic nude rats, forming the basis of this phase I combination study. This study evaluated the toxicity and pharmacokinetics of combining exisulind (150-250 mg) given orally twice daily and docetaxel (30-36 mg/m²) administered i.v. on days 1, 8, and 15 of a 4-wk cycle. Twenty patients with a range of advanced solid tumors (median age, 59 years; age range, 35-77 years; median performance status, 1) received a total of 70 courses. Observed adverse events were mild to moderate, and there was no dose-limiting toxicity at any level. Grade 3 gastrointestinal toxicities were present in 10 of the 70 cycles (10%) and included nausea, vomiting, dyspepsia, and elevated alk. phosphatase. Neutropenia was present in four cycles in patients treated with a docetaxel dose of 36 mg/m². Pharmacokinetic anal. did not demonstrate a clear effect of exisulind on docetaxel pharmacokinetics and vice versa. Relationships were evident between the plasma concentration of exisulind and the development of grade 2 or greater toxicities. One third of patients maintained stable disease for 3 to 12 cycles, but no objective responses were observed The combination of docetaxel (36 mg/m², weekly) and exisulind (500 mg/d) was reasonably well tolerated, and it is undergoing phase II testing in patients with non-small-cell lung cancer.

Clinical Cancer Research published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C19H17N2NaO4S, SDS of cas: 59973-80-7.

Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem

Dawson, Nancy A. published the artcileA phase II study of estramustine, docetaxel, and exisulind in patients with hormone-refractory prostate cancer: results of cancer and leukemia group B trial 90004, Related Products of naphthyridine, the publication is Clinical Genitourinary Cancer (2008), 6(2), 110-116, database is CAplus and MEDLINE.

Docetaxel/estramustine is a known active regimen in hormone-refractory prostate cancer (HRPC). A phase II study was conducted to assess the safety and efficacy of docetaxel/estramustine combined with exisulind, an apoptotic antineoplastic drug. Eighty men with chemotherapy-naive HRPC were enrolled in a multicenter, cooperative group study. The treatment regimen consisted of oral estramustine (280 mg 3 times daily for 5 days), docetaxel 70 mg/m², oral exisulind (250 mg twice daily), oral dexamethasone (8 mg twice daily for 3 days), and oral warfarin (2 mg daily). Seventy-five eligible patients were treated with a median of 6 cycles of therapy. Forty-seven patients (62.7%; 95% CI, 50.7-73.6%) had a â‰?50% decline in prostate-specific antigen levels. Forty-six patients had measurable disease with 6 partial responses (13%; 95% CI, 4.9-26.3%). The main grade 3/4 toxicities were neutrophils (79%), fatigue (15%), and thrombosis/embolism (10%). The median time to first progression was 5.1 mo (95% CI, 4.4-6.3 mo) and the median survival time was 17.8 mo (95% CI, 14.7-20.1 mo). The combination of estramustine/docetaxel/exisulind was associated with significant thomboembolic toxicity despite prophylactic warfarin. The contribution of exisulind to toxicity is uncertain. Prostate-specific antigen decline, response rates, and progression-free and overall survival are similar to those reported with docetaxel/estramustine.

Clinical Genitourinary Cancer published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C20H17FO4S, Related Products of naphthyridine.

Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem

Gardner, S. H. published the artcileEffect of nonsteroidal anti-inflammatory drugs on β-catenin protein levels and catenin-related transcription in human colorectal cancer cells, Recommanded Product: Sulindac sulfone, the publication is British Journal of Cancer (2004), 91(1), 153-163, database is CAplus and MEDLINE.

Elevated β-catenin levels in human colorectal cancer (CRC) cells lead to increased trans-activation of ‘protumorigenic’ β-catenin/T-cell factor (TCF) target genes such as cyclin D1. Therefore, possible targets for the anti-CRC activity of nonsteroidal anti-inflammatory drugs (NSAIDs) are β-catenin and catenin-related transcription (CRT). We tested the antiproliferative activity and the effects on levels of β-catenin and cyclin D1 protein, as well as CRT (measured using a synthetic β-catenin/TCF-reporter gene [TOPflash]), of a panel of NSAIDs (indomethacin, diclofenac, sulindac sulfide and sulfone, rofecoxib; range 10-600 μM) on SW480 human CRC cells in vitro. Following NSAID treatment, there was no consistent relation between reduced cell proliferation, induction of apoptosis and changes in β-catenin protein levels or CRT. All the NSAIDs, except rofecoxib, decreased nuclear β-catenin content and cyclin D1 protein levels in parallel with their antiproliferative activity. However, cyclin D1 down-regulation occurred prior to a decrease in total β-catenin protein levels and there was no correlation with changes in CRT, suggesting the existence of CRT-independent effects of NSAIDs on cyclin D1 expression. In summary, NSAIDs have differential effects on β-catenin protein and CRT, which are unlikely to fully explain their effects on cyclin D1 and their antiproliferative activity on human CRC cells in vitro.

British Journal of Cancer published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C20H17FO4S, Recommanded Product: Sulindac sulfone.

Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem

Liu, Suying published the artcileSulindac derivative-induced apoptosis in a human umbilical vein endothelial cell line ECV304, COA of Formula: C20H17FO4S, the publication is Chinese Medical Journal (Beijing, China, English Edition) (2002), 115(7), 1074-1077, database is CAplus and MEDLINE.

The objective was to investigate the effects of sulindac metabolites on proliferation and apoptosis in the human umbilical vein endothelial cell line ECV304 in vitro. Methods The proliferation profile of ECV304 was determined by Me thiazolyl tetrazolium (MTT) method. Cell cycle distribution, apoptosis, and the ultrastructure of ECV304 were detected by flow cytometry (FCM) and electron microscopy, resp. Results MTT assay showed that the sulfide inhibited the proliferation of ECV304 and its effect was dose-dependent; the IC₅₀ was 200 μmol/L. FCM showed that the sulfide changed cell cycle distribution. The cell cycle distribution was as follows: G₁ phase (control group 77.74%; sulfone group 75.63%; sulfide group 46.12%); S phase (control group 13.64%; sulfone group 16.40; sulfide group 27.26%); G₂-M phase (control group 8.61%; sulfone group 7.98%; sulfide group 26.62%). The apoptosis rates in the control group, sulfone group and sulfide group were 6.08, 4.81, and 51.90%, resp. Sulfide reduced the proportion of G₁ phase, increased the proportion of S phase, G₂-M phase and the apoptosis rate significantly. In the sulfide-treated cells, there were nuclear fragmentation and chromosomal condensation, shrinkage of the cell and loss of contact with neighboring cells. Apoptotic bodies were observed Sulfone showed no effect on cell proliferation, cell cycle distribution, or cell morphol. Conclusions Sulfide can significantly reduce the proliferation of ECV304, change the cell cycle distribution, and arrest cells in G₂-M phase where apoptosis may be induced. Sulfone has no such effects on this cell line.

Chinese Medical Journal (Beijing, China, English Edition) published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C20H17FO4S, COA of Formula: C20H17FO4S.

Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem

Stepnik, M. published the artcileAssessment of the involvement of oxidative stress and Mitogen-Activated Protein Kinase signaling pathways in the cytotoxic effects of arsenic trioxide and its combination with sulindac or its metabolites: sulindac sulfide and sulindac sulfone on human leukemic cell lines, SDS of cas: 59973-80-7, the publication is Medical Oncology (New York, NY, United States) (2012), 29(2), 1161-1172, database is CAplus and MEDLINE.

The purpose of the study was to characterize the involvement of reactive oxygen species (ROS) in mediating the cytotoxic effects of arsenic trioxide (ATO) in combination with sulindac or its metabolites: sulfide (SS) and sulfone (SF) on human leukemic cell lines. Jurkat, HL-60, K562, and HPB-ALL cells were exposed to the drugs alone or in combinations. Cell viability was measured using WST-1 or XTT reduction tests and ROS production by dichlorodihydrofluorescein diacetate staining (flow cytometry). Modulation of (a) intracellular glutathione (GSH) level was done by using l-buthionine sulfoximine (BSO) or diethylmaleate (DEM), (b) NADPH oxidase by using diphenyleneiodonium (DPI), and (c) MAP kinases by using SB202190 (p38), SP600125 (JNK), and U0126 (ERK) inhibitors. ATO cytotoxicity (0.5 or 1 μM) was enhanced by sulindacs, with higher activity showed by the metabolites. Strong cytotoxic effects appeared at SS and SF concentrations starting from 50 μM. The induction of ROS production seemed not to be the major mechanism responsible for the cytotoxicity of the combinations. A strong potentiating effect of BSO on ATO cytotoxicity was demonstrated; DEM (10-300 μM) and DPI (0.0025-0.1 μM; 72 h) did not influence the effects of ATO. Some significant decreases in the viability of the cells exposed to ATO in the presence of MAPK inhibitors comparing with the cells exposed to ATO alone were observed; however, the effects likely resulted from a simple additive cytotoxicity of the drugs. The combinations of ATO with sulindacs offer potential therapeutic usefulness.

Medical Oncology (New York, NY, United States) published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C12H10FeO4, SDS of cas: 59973-80-7.

Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem

Stepnik, Maciej published the artcileSulindac and its metabolites: Sulindac sulfide and sulindac sulfone enhance cytotoxic effects of arsenic trioxide on leukemic cell lines, HPLC of Formula: 59973-80-7, the publication is Toxicology In Vitro (2011), 25(5), 1075-1084, database is CAplus and MEDLINE.

The effects of arsenic trioxide (ATO) in combination with sulindac (SUL), sulindac sulfide (SS) or sulindac sulfone (SF) on human (Jurkat, HL-60, K562 and HPB-ALL) and mouse (EL-4) leukemic cell lines were investigated. The cells showed different sensitivity to sulindacs (2.5-200 μM) with SS being the most cytotoxic (72 h WST-1 reduction test). The cytotoxicity of ATO was enhanced by combination with sulindacs. The combination of ATO (1 μM) with SS or SF at concentrations over 50 μM induced considerable cytotoxicity in all cell lines. Normal human lymphocytes exposed for 48 h to the combinations showed smaller decrease in viability. Measurements of Jurkat, HL-60 and K562 cells exposed to ATO (1 μM) and sulindacs (100 μM or 200 μM for K562 cells) indicated apoptosis as the main cell death mechanism. The mitochondrial membrane potential measurements (JC-1 probe) indicated an active involvement of mitochondria in the process. The results did not indicate involvement of an inhibitory effect of the combinations on NF-κB activity in Jurkat, HL-60 and K562 cells.

Toxicology In Vitro published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C12H25Br, HPLC of Formula: 59973-80-7.

Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem

Chi, Xiuling published the artcile15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is up-regulated by flurbiprofen and other non-steroidal anti-inflammatory drugs in human colon cancer HT29 cells, Related Products of naphthyridine, the publication is Archives of Biochemistry and Biophysics (2009), 487(2), 139-145, database is CAplus and MEDLINE.

Non-steroidal anti-inflammatory drugs (NSAIDs) are known to inhibit prostaglandin synthetic enzyme, cyclooxygenases (COXs), as well as to exhibit anti-tumor activity although at much higher concentrations 15-Hydroxyprostaglandin dehydrogenase (15-PGDH), a key prostaglandin catabolic enzyme, was recently shown to be a tumor suppressor. Effects of NSAIDs on 15-PGDH expression were therefore examined Flurbiprofen and several other NSAIDs were found to induce 15-PGDH expression in human colon cancer HT29 cells. Flurbiprofen, the most active one, was also shown to induce 15-PGDH expression in other types of cancer cells. Induction of 15-PGDH expression appeared to occur at the stage of mRNA as levels of 15-PGDH mRNA were increased by flurbiprofen in HT29 cells. Levels of 15-PGDH were also found to be regulated at the stage of protein turnover. MEK inhibitors, PD98059 and U-0126, which inhibited ERK phosphorylation were shown to elevate 15-PGDH levels very significantly. These inhibitors did not appear to alter 15-PGDH mRNA levels but down-regulate matrix metalloproteinase-9 (MMP-9). This protease was shown to degrade and inactivate 15-PGDH suggesting that elevation of 15-PGDH levels could be due to inhibition of MMP-9 expression by these inhibitors. Similarly, flurbiprofen was also demonstrated to inhibit ERK activation and to down-regulate MMP-9 expression. Furthermore, flurbiprofen was shown to induce the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), an inhibitor of MMP-9. The turnover of 15-PGDH was found to prolong in the presence of flurbiprofen as compared to that in the absence of this drug. Taken together, these results indicate that flurbiprofen up-regulates 15-PGDH by increasing the expression and decreasing the degradation of 15-PGDH in HT29 cells.

Archives of Biochemistry and Biophysics published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C20H17FO4S, Related Products of naphthyridine.

Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem

Tinsley, Heather N. published the artcileColon tumor cell growth-inhibitory activity of sulindac sulfide and other nonsteroidal anti-inflammatory drugs is associated with phospphodiesterase 5 inhibition, Synthetic Route of 59973-80-7, the publication is Cancer Prevention Research (2010), 3(10), 1303-1313, database is CAplus and MEDLINE.

Nonsteroidal anti-inflammatory drugs (NSAID) display promising antineoplastic activity, but toxicity resulting from cyclooxygenase (COX) inhibition limits their clin. use for chemoprevention. Studies suggest that the mechanism may be COX independent, although alternative targets have not been well defined. Here, we show that the NSAID sulindac sulfide (SS) inhibits cyclic guanosine 3′,5′-monophosphate (cGMP) phosphodiesterase (PDE) activity in colon tumor cell lysates at concentrations that inhibit colon tumor cell growth in vitro and in vivo. A series of chem. diverse NSAIDs also inhibited cGMP hydrolysis at concentrations that correlate with their potency to inhibit colon tumor cell growth, whereas no correlation was observed with COX-2 inhibition. Consistent with its selectivity for inhibiting cGMP hydrolysis compared with cAMP hydrolysis, SS inhibited the cGMP-specific PDE5 isoenzyme and increased cGMP levels in colon tumor cells. Of numerous PDE isoenzyme-specific inhibitors evaluated, only the PDE5-selective inhibitor MY5445 inhibited colon tumor cell growth. The effects of SS and MY5445 on cell growth were associated with inhibition of β-catenin-mediated transcriptional activity to suppress the synthesis of cyclin D and survivin, which regulate tumor cell proliferation and apoptosis, resp. SS had minimal effects on cGMP PDE activity in normal colonocytes, which displayed reduced sensitivity to SS and did not express PDE5. PDE5 was found to be overexpressed in colon tumor cell lines as well as in colon adenomas and adenocarcinomas compared with normal colonic mucosa. These results suggest that PDE5 inhibition, cGMP elevation, and inhibition of β-catenin transcriptional activity may contribute to the chemopreventive properties of certain NSAIDs.

Cancer Prevention Research published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C9H16BNO2, Synthetic Route of 59973-80-7.

Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem