The Experts below are selected from a list of 90 Experts worldwide ranked by ideXlab platform
Thomayant Prueksaritanont - One of the best experts on this subject based on the ideXlab platform.
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nonpeptide αvβ3 antagonists part 10 in vitro and in vivo evaluation of a potent 7 methyl substituted tetrahydro 1 8 Naphthyridine Derivative
Bioorganic & Medicinal Chemistry Letters, 2004Co-Authors: Michael J Breslin, Mark E Duggan, Wasyl Halczenko, George D Hartman, Le T Duong, Carmen Fernandezmetzler, Michael A Gentile, Donald B Kimmel, Kara Merkle, Thomayant PrueksaritanontAbstract:Abstract Subtle modifications were incorporated into the structure of clinical candidate 1 . These changes were designed to maintain potency and selectivity while inducing changes in physical properties leading to improved pharmacokinetics in three species. This approach led to the identification of 4 as a potent, selective α v β 3 receptor antagonist that was selected for clinical development based on an improved PK profile and efficacy demonstrated in an in vivo model of bone turnover.
Seiichi Nishizawa - One of the best experts on this subject based on the ideXlab platform.
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Chloro-Substituted Naphthyridine Derivative and Its Conjugate with Thiazole Orange for Highly Selective Fluorescence Sensing of an Orphan Cytosine in the AP Site-Containing Duplexes
Applied Sciences, 2020Co-Authors: Chun-xia Wang, Norio Teramae, Yusuke Sato, Takashi Sugimoto, Seiichi NishizawaAbstract:Fluorescent probes with the binding selectivity to specific structures in DNAs or RNAs have gained much attention as useful tools for the study of nucleic acid functions. Here, chloro-substituted 2-amino-5,7-dimethyl-1,8-Naphthyridine (ClNaph) was developed as a strong and highly selective binder for target orphan cytosine opposite an abasic (AP) site in the DNA duplexes. ClNaph was then conjugated with thiazole orange (TO) via an alkyl spacer (ClNaph–TO) to design a light-up probe for the detection of cytosine-related mutations in target DNA. In addition, we found the useful binding and fluorescence signaling of the ClNaph–TO conjugate to target C in AP site-containing DNA/RNA hybrid duplexes with a view toward sequence analysis of microRNAs.
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fluorescent trimethylated Naphthyridine Derivative with an aminoalkyl side chain as the tightest non aminoglycoside ligand for the bacterial a site rna
Chemistry: A European Journal, 2018Co-Authors: Yusuke Sato, Norio Teramae, Masafumi Rokugawa, Sayaka Yajima, Hiroki Sugawara, Seiichi NishizawaAbstract:: The bacterial ribosomal decoding region of the aminoacyl-tRNA site (A-site) is one of the most validated target RNAs for antibiotic agents. Although natural aminoglycosides are well-characterized A-site binding ligands, high off-target effects and the growing emergence of bacterial resistance against aminoglycosides limit their clinical use. To circumvent these concerns with the aminoglycoside family, non-aminoglycoside A-site binding ligands have great potential as novel antibiotics against bacterial infections. This work describes a new class of small heterocyclic ligands based on the 2-amino-5,6,7-trimethyl-1,8-Naphthyridine (ATMND) structure for the bacterial (Escherichia coli) A-site. ATMND possessing an aminoethyl side chain is found to strongly and selectively bind to the internal loop of the A-site (Kd =0.44 μm; pH 7.0, I=0.06 m, 5 °C). Significantly, this ligand shows the tightest binding reported to date among non-aminoglycoside ligands. The binding study based on the thermodynamics and molecular modelling reveals key molecular interactions of ATMND-C2 -NH2 for high affinity to the A-site. This ligand is also demonstrated to be applicable to the fluorescence indicator displacement assay for assessing ligand/A-site interactions.
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Effect of an alkyl amino group on the binding of 1,8-Naphthyridines to AP site-containing DNA duplexes.
Nucleic Acids Symposium Series, 2008Co-Authors: Toshiki Ichihashi, Yusuke Sato, Seiichi Nishizawa, Takehiro Seino, Norio TeramaeAbstract:: A 1,8-Naphthyridine Derivative having a positively charged side-chain, N-(3-aminopropyl)-5,6,7-trimethyl-1,8-Naphthyridine-2-amine (APATMND), is synthesized, and its binding to AP site-containing DNA duplexes (5'- GCA GCT CCC GXG GTC TCC TCG-3'/ 5'-CGA GGA GAC CNC GGG AGC TGC-3', X = AP site; dSpacer, N = C, T) is examined in solutions buffered to pH 7.0 (I = 0.11 M, at 20 degrees C). Fluorescence titration experiments reveal that, as compared to a parent ligand, 2-amino-5,6,7-trimethyl-1,8-Naphthyridine (ATMND), capable of selectively binding C over T opposite an AP site in the duplex (K(d)/nM: C: 56, T: 100), APATMND shows a stronger binding affinity for T, while an affinity for C is reduced (K(d)/nM: C: 135, T: 37). An examination of salt dependence of binding constants reveals that a polyelectrolyte contribution (Delta G(pe)) is indeed increased for C- and T-bindings of APATMND, but a loss of non-polyelectrolyte contribution (Delta G(t)) is significant when binding to C. These binding properties of APATMND are discussed with a view towards further development of DNA-binding ligands suitable for gene detection.
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electrochemical and fluorescence detection of cytosine related snps using a ferrocenyl Naphthyridine Derivative
Nucleic acids symposium series (2004), 2007Co-Authors: Kotaro Morita, Yusuke Sato, Seiichi Nishizawa, Takehiro Seino, Norio TeramaeAbstract:: A novel hydrogen bond-forming ligand for cytosine-related single nucleotide polymorphism, which contains both a fluorescent Naphthyridine moiety and a ferrocene group as an electrochemical indicator, is described. Hydrogen bond-mediated recognition for a target nucleobase within an abasic site-containing DNA duplex was confirmed by both fluorescence and electrochemical measurements. The analysis by fluorescence titration reveals that the ligand shows significant fluorescent quenching upon formation of a 1: 1 complex with the target nucleobase opposite an AP site, and the selectivity was in the order of cytosine > thymine > adenine, guanine, reflecting the stability of hydrogen bond formation.
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ratiometric fluorescence detection of pyrimidine purine transversion by using a 2 amino 1 8 Naphthyridine Derivative
Analytical Sciences, 2006Co-Authors: Hiroyuki Satake, Seiichi Nishizawa, Norio TeramaeAbstract:A new class of abasic site-binding fluorescence ligands, Naph-NBD in which 7-nitrobenzo-2-oxa-1,3-diazole (NBD) is connected to 2-amino-7-methyl-1,8-Naphthyridine (Naph) by a propylene linker, is presented for the ratiometric assay for SNPs typing. In solutions buffered to pH 7.0 (I = 0.11 M, at 5°C), Naph-NBD is found to selectively recognize pyrimidine bases over purine bases opposite the abasic site in DNA duplexes (K11/M-1: T, 8.1 × 106; C, 2.5 × 106; G, 0.33 × 106; A, 0.27 × 106). The binding of Naph-NBD is accompanied by significant quenching of the fluorescence from the Naphthyridine moiety (λmax, 409 nm), while the emission from the NBD (λmax, 544 nm) is relatively unaffected. Such a fluorescence response of Naph-NBD allows the emission ratio detection of pyrimidine/purine transversion.
Jiaxu Zhang - One of the best experts on this subject based on the ideXlab platform.
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influences of enhanced conjugated framework on the structures and photophysical properties of bf2 core compounds containing 1 8 Naphthyridine Derivative a dft td dft study
Optical Materials, 2018Co-Authors: Jianfei Wang, Hongyan Ning, Li Yang, Jiaxu ZhangAbstract:Abstract We have studied the structural and photophysical characteristics of a series of 1,8-Naphthyridine-BF2 compounds in detail. The purpose of quantum-chemical calculations is to study the effect of electron-withdrawing (electron-donating) substituents and core-frame conjugation on the optical properties. The solvent effects are researched in toluene, CH2Cl2, THF, acetone, CH3CN and CH3OH solutions, respectively, by polarizable continuum model (PCM). The results show that the HOMO, LUMO, energy gaps, IP and EA of BF2 core compounds 1–3 containing 1,8-Naphthyridine change regularly due to the different degrees of conjugation framework. However, the influence of the substituent changes on these molecules is not significant. The results also show that the maximum absorption wavelengths of the complexes exhibit blue shift as the polarity of the solvent increases from toluene to CH3OH. In addition, the absorption wavelengths of the studied molecules are red-shifted to some extent due to the increased conjugation in the central framework. All calculations reveal that the Naphthyridine-BF2 compounds are expected to be a useful luminescent material for OLEDs.
Manu Jaggi - One of the best experts on this subject based on the ideXlab platform.
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anti inflammatory activity of a Naphthyridine Derivative 7 chloro 6 fluoro n 2 hydroxy 3 oxo 1 phenyl 3 phenylamino propyl 4 oxo 1 prop 2 yn 1 yl 1 4 dihydro 1 8 Naphthyridine 3 carboxamide possessing in vitro anticancer potential
International Immunopharmacology, 2013Co-Authors: Alka Madaan, Vivek Kumar, Ritu Verma, Anu T Singh, S K Jain, Manu JaggiAbstract:Abstract We have previously synthesized a series of 1,8-Naphthyridine-3-carboxamide Derivatives to identify potential anti-cancer/anti-inflammatory compounds. Three Derivatives, 7-chloro- N -(3-(cyclopentylamino)-3-oxo-1-phenylpropyl)-6-fluoro-4-oxo-1-(prop-2-yn-1-yl)-1,4-dihydro-1,8-Naphthyridine-3-carboxamide (C-22), 7-chloro- N -(2-hydroxy-3-oxo-1-phenyl-3-(phenylamino)propyl)-4-oxo-1-(prop-2-yn-1-yl)-1,4-dihydro-1,8-Naphthyridine-3-carboxamide (C-31) and 7-chloro-6-fluoro- N -(2-hydroxy-3-oxo-1-phenyl-3-(phenylamino)propyl)-4-oxo-1-(prop-2-yn-1-yl)-1,4-dihydro-1,8-Naphthyridine-3-carboxamide (C-34) demonstrated high cytotoxicity against a number of cancer cell lines and inhibited secretion of IL-1-β and IL-6. In the present study, C-22, C-31 and C-34 were assessed for modulation of pro-inflammatory cytokines, TNF-α and IL-8, chemokine RANTES and NO produced by lipopolysaccharide (LPS)-treated mouse Dendritic cells (DCs). Among the 3 compounds, C-34 showed the most potent inhibition of inflammatory markers in DC model at 0.2 and 2 μM. C-34 also significantly downregulated the secretion of TNF-α, IL-1-β and IL-6 by murine splenocytes and THP-1 cells against LPS induced levels. In vitro effects of C-34 on bone marrow toxicity were assessed in CFU-GM assay. Human CFU-GM population was comparatively more sensitive to C-34 (0.1–10 μM) than murine CFU-GM. IC 50 values for murine and human CFU-GM were not attained. C-34 was further examined for in vivo suppression of LPS induced cytokines in a mice model. At doses ranging from 1.25 to 5 mg/kg, C-34 led to significant inhibition of TNF-α, IL-1-β, IL-6 and MIP-1-α. At the highest dose of 5 mg/kg, C-34 also protected LPS-treated mice against endotoxin-induced lethality. In conclusion, C-34 demonstrates anti-inflammatory activity in vitro and in vivo in addition to cytotoxic properties. This finding suggests its potential for further development as a synthetic Naphthyridine Derivative with dual anti-cancer and anti-inflammatory (cytokine inhibition) properties.
Norio Teramae - One of the best experts on this subject based on the ideXlab platform.
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Chloro-Substituted Naphthyridine Derivative and Its Conjugate with Thiazole Orange for Highly Selective Fluorescence Sensing of an Orphan Cytosine in the AP Site-Containing Duplexes
Applied Sciences, 2020Co-Authors: Chun-xia Wang, Norio Teramae, Yusuke Sato, Takashi Sugimoto, Seiichi NishizawaAbstract:Fluorescent probes with the binding selectivity to specific structures in DNAs or RNAs have gained much attention as useful tools for the study of nucleic acid functions. Here, chloro-substituted 2-amino-5,7-dimethyl-1,8-Naphthyridine (ClNaph) was developed as a strong and highly selective binder for target orphan cytosine opposite an abasic (AP) site in the DNA duplexes. ClNaph was then conjugated with thiazole orange (TO) via an alkyl spacer (ClNaph–TO) to design a light-up probe for the detection of cytosine-related mutations in target DNA. In addition, we found the useful binding and fluorescence signaling of the ClNaph–TO conjugate to target C in AP site-containing DNA/RNA hybrid duplexes with a view toward sequence analysis of microRNAs.
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fluorescent trimethylated Naphthyridine Derivative with an aminoalkyl side chain as the tightest non aminoglycoside ligand for the bacterial a site rna
Chemistry: A European Journal, 2018Co-Authors: Yusuke Sato, Norio Teramae, Masafumi Rokugawa, Sayaka Yajima, Hiroki Sugawara, Seiichi NishizawaAbstract:: The bacterial ribosomal decoding region of the aminoacyl-tRNA site (A-site) is one of the most validated target RNAs for antibiotic agents. Although natural aminoglycosides are well-characterized A-site binding ligands, high off-target effects and the growing emergence of bacterial resistance against aminoglycosides limit their clinical use. To circumvent these concerns with the aminoglycoside family, non-aminoglycoside A-site binding ligands have great potential as novel antibiotics against bacterial infections. This work describes a new class of small heterocyclic ligands based on the 2-amino-5,6,7-trimethyl-1,8-Naphthyridine (ATMND) structure for the bacterial (Escherichia coli) A-site. ATMND possessing an aminoethyl side chain is found to strongly and selectively bind to the internal loop of the A-site (Kd =0.44 μm; pH 7.0, I=0.06 m, 5 °C). Significantly, this ligand shows the tightest binding reported to date among non-aminoglycoside ligands. The binding study based on the thermodynamics and molecular modelling reveals key molecular interactions of ATMND-C2 -NH2 for high affinity to the A-site. This ligand is also demonstrated to be applicable to the fluorescence indicator displacement assay for assessing ligand/A-site interactions.
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Effect of an alkyl amino group on the binding of 1,8-Naphthyridines to AP site-containing DNA duplexes.
Nucleic Acids Symposium Series, 2008Co-Authors: Toshiki Ichihashi, Yusuke Sato, Seiichi Nishizawa, Takehiro Seino, Norio TeramaeAbstract:: A 1,8-Naphthyridine Derivative having a positively charged side-chain, N-(3-aminopropyl)-5,6,7-trimethyl-1,8-Naphthyridine-2-amine (APATMND), is synthesized, and its binding to AP site-containing DNA duplexes (5'- GCA GCT CCC GXG GTC TCC TCG-3'/ 5'-CGA GGA GAC CNC GGG AGC TGC-3', X = AP site; dSpacer, N = C, T) is examined in solutions buffered to pH 7.0 (I = 0.11 M, at 20 degrees C). Fluorescence titration experiments reveal that, as compared to a parent ligand, 2-amino-5,6,7-trimethyl-1,8-Naphthyridine (ATMND), capable of selectively binding C over T opposite an AP site in the duplex (K(d)/nM: C: 56, T: 100), APATMND shows a stronger binding affinity for T, while an affinity for C is reduced (K(d)/nM: C: 135, T: 37). An examination of salt dependence of binding constants reveals that a polyelectrolyte contribution (Delta G(pe)) is indeed increased for C- and T-bindings of APATMND, but a loss of non-polyelectrolyte contribution (Delta G(t)) is significant when binding to C. These binding properties of APATMND are discussed with a view towards further development of DNA-binding ligands suitable for gene detection.
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electrochemical and fluorescence detection of cytosine related snps using a ferrocenyl Naphthyridine Derivative
Nucleic acids symposium series (2004), 2007Co-Authors: Kotaro Morita, Yusuke Sato, Seiichi Nishizawa, Takehiro Seino, Norio TeramaeAbstract:: A novel hydrogen bond-forming ligand for cytosine-related single nucleotide polymorphism, which contains both a fluorescent Naphthyridine moiety and a ferrocene group as an electrochemical indicator, is described. Hydrogen bond-mediated recognition for a target nucleobase within an abasic site-containing DNA duplex was confirmed by both fluorescence and electrochemical measurements. The analysis by fluorescence titration reveals that the ligand shows significant fluorescent quenching upon formation of a 1: 1 complex with the target nucleobase opposite an AP site, and the selectivity was in the order of cytosine > thymine > adenine, guanine, reflecting the stability of hydrogen bond formation.
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ratiometric fluorescence detection of pyrimidine purine transversion by using a 2 amino 1 8 Naphthyridine Derivative
Analytical Sciences, 2006Co-Authors: Hiroyuki Satake, Seiichi Nishizawa, Norio TeramaeAbstract:A new class of abasic site-binding fluorescence ligands, Naph-NBD in which 7-nitrobenzo-2-oxa-1,3-diazole (NBD) is connected to 2-amino-7-methyl-1,8-Naphthyridine (Naph) by a propylene linker, is presented for the ratiometric assay for SNPs typing. In solutions buffered to pH 7.0 (I = 0.11 M, at 5°C), Naph-NBD is found to selectively recognize pyrimidine bases over purine bases opposite the abasic site in DNA duplexes (K11/M-1: T, 8.1 × 106; C, 2.5 × 106; G, 0.33 × 106; A, 0.27 × 106). The binding of Naph-NBD is accompanied by significant quenching of the fluorescence from the Naphthyridine moiety (λmax, 409 nm), while the emission from the NBD (λmax, 544 nm) is relatively unaffected. Such a fluorescence response of Naph-NBD allows the emission ratio detection of pyrimidine/purine transversion.
