The Experts below are selected from a list of 543 Experts worldwide ranked by ideXlab platform
Fanizzi, Francesco Paolo - One of the best experts on this subject based on the ideXlab platform.
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Novel Antiproliferative Biphenyl Nicotinamide:NMR Metabolomic Study of its Effect on the MCF-7 Cell in Comparison with Cisplatin and Vinblastine
'MDPI AG', 2020Co-Authors: Del Coco Laura, Majellaro Maria, Boccarelli Angelina, Cellamare Saverio, Altomare, Cosimo Damiano, Fanizzi, Francesco PaoloAbstract:A 1H-NMR-based metabolomic study was performed on MCF-7 cell lines treated with a novel Nicotinamide Derivative (DT-8) in comparison with two drugs characterized by a wellestablished mechanism of action, namely the DNA-metalating drug cisplatin (cisdiamminedichloridoplatinum(II), CDDP) and the antimitotic drug vinblastine (vinblastine, VIN). The effects of the three compounds, each one at the concentration corresponding to the IC50 value, were investigated, with respect to the controls (K), by the 1H-NMR of cells lysates and multivariate analysis (MVA) of the spectroscopic data. Relevant differences were found in the metabolic profiles of the different treatments with respect to the controls. A large overlap of the metabolic profiles in DT-8 vs. K and VIN vs. K suggests a similar biological response and mechanism of action, significantly diverse with respect to CDDP. On the other hand, DT8 seems to act by disorganizing the mitotic spindle and ultimately blocking the cell division, through a mechanism implying methionine depletion and/or S-adenosylmethionine (SAM) limitation
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Novel Antiproliferative Biphenyl Nicotinamide: NMR Metabolomic Study of its Effect on the MCF-7 Cell in Comparison with Cisplatin and Vinblastine
'MDPI AG', 2020Co-Authors: Coco, Laura Del, Majellaro Maria, Boccarelli Angelina, Cellamare Saverio, Altomare, Cosimo Damiano, Fanizzi, Francesco PaoloAbstract:A 1H-NMR-based metabolomic study was performed on MCF-7 cell lines treated with a novel Nicotinamide Derivative (DT-8) in comparison with two drugs characterized by a well-established mechanism of action, namely the DNA-metalating drug cisplatin (cis-diamminedichloridoplatinum(II), CDDP) and the antimitotic drug vinblastine (vinblastine, VIN). The effects of the three compounds, each one at the concentration corresponding to the IC50 value, were investigated, with respect to the controls (K), by the 1H-NMR of cells lysates and multivariate analysis (MVA) of the spectroscopic data. Relevant differences were found in the metabolic profiles of the different treatments with respect to the controls. A large overlap of the metabolic profiles in DT-8 vs. K and VIN vs. K suggests a similar biological response and mechanism of action, significantly diverse with respect to CDDP. On the other hand, DT8 seems to act by disorganizing the mitotic spindle and ultimately blocking the cell division, through a mechanism implying methionine depletion and/or S-adenosylmethionine (SAM) limitationThis research was funded by PRIN, Grant 201744BN5T_004S
Tatsuki Koike - One of the best experts on this subject based on the ideXlab platform.
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discovery of novel 4 phenyl 2 pyrrolidinyl Nicotinamide Derivatives as potent nav1 1 activators
Bioorganic & Medicinal Chemistry Letters, 2019Co-Authors: Tohru Miyazaki, Masanori Kawasaki, Atsushi Suzuki, Yuki Ito, Akio Imanishi, Takamitsu Maru, Tomohiro Kawamoto, Tatsuki KoikeAbstract:Abstract The voltage-gated sodium channel, Nav1.1, is predominantly expressed in parvalbumin-positive fast spiking interneurons and has been genetically linked to Dravet syndrome. Starting from a high throughput screening hit isoxazole Derivative 5, modifications of 5 via combinations of IonWorks and Q-patch assays successfully identified the Nicotinamide Derivative 4. Its increasing decay time constant (tau) of Nav1.1 currents at 0.03 μM along with significant selectivity against Nav1.2, Nav1.5, and Nav1.6 and acceptable brain exposure in mice was observed. Compound 4 is a promising Nav1.1 activator that can be used to analyze pathophysiological functions of the Nav1.1 channel towards treating various central nervous system diseases.
Mcdermott Walsh - One of the best experts on this subject based on the ideXlab platform.
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MICROBIAL PERSISTENCE : I. THE CAPACITY OF TUBERCLE BACILLI TO SURVIVE STERILIZATION IN MOUSE TISSUES
The Rockefeller University Press, 2026Co-Authors: Mccune, Robert M., Feldmann, Floyd M., Lambert, Harold P., Mcdermott WalshAbstract:A previously reported form of microbial persistence whereby large populations of tubercle bacilli can be made to "vanish" uniformly from the tissues of mice has been shown to occur generally throughout each group of animals subjected to the experimental procedure; it does not reflect the eradication of the bacilli in the majority of animals with their persistence and ultimate revival in only a minority. The one demonstrable alteration of the tubercle bacilli while "vanished" is that they are sterile. Thus, they are undetectable by cell-free culture, tissue culture, and blind animal passage, i.e. by any method based on microbial multiplication. Whether they have also undergone alteration in morphology and persist in some unconventional form cannot be stated. Acid-fast forms similar to tubercle bacilli can be detected in small numbers by intensified microscopic search of tissue homogenates but the relationship of these forms to the sterile bacilli that ultimately revive is unclear. Thus, the persisting tubercle bacilli are more correctly designated as being in a "sterile state" than one of true latency. The uniform induction of the sterile state is a specific phenomenon requiring the participation of both the Nicotinamide Derivative, pyrazinamide, and isoniazid. Once assumed, this sterile state is relatively stable and the time required for revival of the tubercle bacilli in the spleens in one-half the animals is seven months. This process can be speeded up by the administration of large doses of cortisone in the third or fourth month after sterilization but revival is not significantly affected by the administration of cortisone earlier
Leandro F S Bastos - One of the best experts on this subject based on the ideXlab platform.
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activity of nicorandil a Nicotinamide Derivative with a nitrate group in the experimental model of pain induced by formaldehyde in mice
Pharmacology Biochemistry and Behavior, 2013Co-Authors: Marcela M G B Dutra, Adriana M Godin, Isabela Costa Cesar, Elias B Nascimento, Raquel R Menezes, Wallace C Ferreira, Darly G Soares, Joao Gabriel T Seniuk, Debora P Araujo, Leandro F S BastosAbstract:Nicorandil (2-Nicotinamide ethyl nitrate), an antianginal drug characterized by the coupling of Nicotinamide with a nitric oxide (NO) donor, activates guanylyl cyclase and opens ATP-dependent K(+) channels. In the present study, we investigated the effects induced by per os (p.o.) administration of nicorandil (12.5, 25 or 50 mg/kg) or equimolar doses (corresponding to the highest dose of nicorandil) of N-(2-hydroxyethyl) Nicotinamide (NHN), its main metabolite, or Nicotinamide in the model of nociceptive response induced by formaldehyde in mice. Nicorandil, but not NHN or Nicotinamide, inhibited the second phase of the nociceptive response. This activity was observed when nicorandil was administered between 30 and 120 min before the injection of formaldehyde. Ipsilateral intraplantar injection of nicorandil (125, 250 or 500 μg/paw) did not inhibit the nociceptive response. After p.o. administration of nicorandil (50 mg/kg), peak plasma concentrations of this compound and NHN were observed 0.63 and 4 h later, respectively. Nicotinamide concentrations were not increased after administration of nicorandil. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 1 or 2 mg/kg), a guanylyl cyclase inhibitor, partially attenuated the antinociceptive activity of nicorandil. However, this activity was not changed by glibenclamide (30 or 60 mg/kg), an inhibitor of ATP-dependent K(+) channels. In conclusion, we demonstrated the antinociceptive activity of nicorandil in a model of pain that exhibits both a nociceptive and an inflammatory profile. This activity is not mediated by Nicotinamide or NHN. The coupling of an NO-donor to Nicotinamide results in a compound with an increased potency. The NO-cGMP pathway, but not ATP-dependent K(+) channels, partially mediates the antinociceptive activity of nicorandil.
Tadahiro Kitamura - One of the best experts on this subject based on the ideXlab platform.
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protective effects of a Nicotinamide Derivative isoNicotinamide against streptozotocin induced β cell damage and diabetes in mice
Biochemical and Biophysical Research Communications, 2013Co-Authors: Makiko Fukaya, Yoshiaki Tamura, Yuko Chiba, Toshihiro Tanioka, Ji Mao, Yoko Inoue, Marina Yamada, Christian Waeber, Yukari Idokitamura, Tadahiro KitamuraAbstract:Abstract Objective Nicotinamide rescues β-cell damage and diabetes in rodents, but a large-scale clinical trial failed to show the benefit of Nicotinamide in the prevention of type 1 diabetes. Recent studies have shown that Sirt1 deacetylase, a putative protector of β-cells, is inhibited by Nicotinamide. We investigated the effects of isoNicotinamide, which is a Derivative of Nicotinamide and does not inhibit Sirt1, on streptozotocin (STZ)-induced diabetes in mice. Research design and methods Male C57BL/6 mice were administered with three different doses of STZ (65, 75, and 100 mg/kg BW) alone or in combination with subsequent high-fat feeding. The mice were treated with isoNicotinamide (250 mg/kg BW/day) or phosphate-buffered saline for 10 days. The effects of isoNicotinamide on STZ-induced diabetes were assessed by blood glucose levels, glucose tolerance test, and immunohistochemistry. Results IsoNicotinamide effectively prevented hyperglycemia induced by higher doses of STZ (75 and 100 mg/kg BW) alone and low-dose STZ (65 mg/kg BW) followed by 6-week high-fat diet in mice. The protective effects of isoNicotinamide were associated with decreased apoptosis of β-cells and reductions in both insulin content and insulin-positive area in the pancreas of STZ-administered mice. In addition, isoNicotinamide inhibited STZ-induced apoptosis in cultured isolated islets. Conclusions These data clearly demonstrate that isoNicotinamide exerts anti-diabetogenic effects by preventing β-cell damage after STZ administration. These findings warrant further investigations on the protective effects of isoNicotinamide and related compounds against β-cell damage in diabetes.