39 results on '"benzonaphthyridine"'
Search Results
2. Synthesis of Novel Benzo[b][1,6]naphthyridine Derivatives and Investigation of Their Potential as Scaffolds of MAO Inhibitors
- Author
-
Larisa N. Kulikova, Ghulam Reza Raesi, Daria D. Levickaya, Rosa Purgatorio, Gabriella La Spada, Marco Catto, Cosimo D. Altomare, and Leonid G. Voskressensky
- Subjects
benzonaphthyridine ,activated alkynes ,MAO inhibitors ,Alzheimer’s disease ,Organic chemistry ,QD241-441 - Abstract
In this work, 2-alkyl-10-chloro-1,2,3,4-tetrahydrobenzo[b][1,6]naphthyridines were obtained and their reactivity was studied. Novel derivatives of the tricyclic scaffold, including 1-phenylethynyl (5), 1-indol-3-yl (8), and azocino[4,5-b]quinoline (10) derivatives, were synthesized and characterized herein for the first time. Among the newly synthesized derivatives, 5c–h proved to be MAO B inhibitors with potency in the low micromolar range. In particular, the 1-(2-(4-fluorophenyl)ethynyl) analog 5g achieved an IC50 of 1.35 μM, a value close to that of the well-known MAO B inhibitor pargyline.
- Published
- 2023
- Full Text
- View/download PDF
3. Combined 3D-QSAR and Molecular Docking Study on benzo[h][1,6]naphthyridin-2(1H)-one Analogues as mTOR Inhibitors.
- Author
-
WANG, B., LIU, M. M., WANG, B. W., and LIN, Z. H.
- Subjects
- *
QSAR models , *MOLECULAR docking , *BENZONAPHTHYRIDINE , *MTOR inhibitors , *MOLECULAR structure - Abstract
Mechanistic target of rapamycin is involved in the formation of tumor microvasculature was an ideal target for computer-aided drug design. The predictive study of quantitative structure-activity relationship and molecular docking can shorten the cycle and reduce the cost of designing the higher activity mTOR inhibitors. In this article, comparative molecular field analysis and comparative molecular similarity indices analysis fields were used to analyse three-dimensional quantitative structure-activity relationship model. The model (comparative molecular similarity indices analysis with q2=0.607, r2=0.909; comparative molecular similarity indices analysis with q2=0.703, r2=0.935) has a good predictability. Three-dimensional quantitative structure-activity relationship model contour maps indicate the electrostatic, hydrophobic and hydrogen bond donor fields have crucial effects to derivatives biological activity. Molecular docking was employed to explore the conformations of 55 compounds with key amino acid residues. Finally, combining contour maps with molecular docking results, ten derivatives as potential mechanistic target of rapamycin inhibitors were designed to further verify established three-dimensional quantitative structure-activity relationship models. These data provide significant theoretical foundation for designing better activity mechanistic target of rapamycin inhibitors. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
4. Structure-activity relationship investigation for benzonaphthyridinone derivatives as novel potent Bruton's tyrosine kinase (BTK) irreversible inhibitors.
- Author
-
Wang, Beilei, Deng, Yuanxin, Chen, Yongfei, Yu, Kailin, Wang, Aoli, Liang, Qianmao, Wang, Wei, Chen, Cheng, Wu, Hong, Hu, Chen, Miao, Weili, Hur, Wooyoung, Wang, Wenchao, Hu, Zhenquan, Weisberg, Ellen L., Wang, Jinhua, Ren, Tao, Wang, Yinsheng, Gray, Nathanael S., and Liu, Qingsong
- Subjects
- *
STRUCTURE-activity relationship in pharmacology , *BENZONAPHTHYRIDINE , *DRUG design , *CHEMICAL derivatives - Abstract
Through a structure-based drug design approach, a tricyclic benzonaphthyridinone pharmacophore was used as a starting point for carrying out detailed medicinal structure-activity relationhip (SAR) studies geared toward characterization of a panel of proposed BTK inhibitors, including 6 (QL-X-138), 7 (BMX-IN-1) and 8 (QL47). These studies led to the discovery of the novel potent irreversible BTK inhibitor, compound 18 (CHMFL-BTK-11). Kinetic analysis of compound 18 revealed an irreversible binding efficacy ( k inact /K i ) of 0.01 μM −1 s −1 . Compound 18 potently inhibited BTK kinase Y223 auto-phosphorylation (EC 50 < 100 nM), arrested cell cycle in G0/G1 phase, and induced apoptosis in Ramos, MOLM13 and Pfeiffer cells. We believe these features would make 18 a good pharmacological tool for studying BTK-related pathologies. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
5. Synthesis and Anti-Intestinal Nematode Activity of Variously Substituted Benzonaphthyridine Derivatives
- Author
-
Ai-Dan Wen, Yi Tao, Ning-Bo Wu, Li-Ping Duan, and Hao-Bing Zhang
- Subjects
benzonaphthyridine ,C=N linkage ,Nippostrongylus brazilliensis ,Organic chemistry ,QD241-441 - Abstract
A series of benzonaphthyridine derivatives bearing the C=N linkage moiety were designed and synthesized. The structures of all the newly synthesized compounds were identified by elemental analysis, 1H-NMR, 13C-NMR and MS. Their anti-intestinal nematode activities against Nippostrongylus brazilliensis were evaluated in vivo by an oral route in male rats. Among these compounds, at concentrations of 10 mg/kg of rat, the compound 7-chloro-2-methoxy-10-(4-(4′-(1H-indol-5′-yl)methylene)aminophenyl)-amino-benzo[b][1,5] naphthyridine (4n) produced the highest activity, with 80.2% deparasitization. These compounds may find usefulness in the discovery and development of new anti-intestinal drugs.
- Published
- 2011
- Full Text
- View/download PDF
6. Incorporation of Phosphonate into Benzonaphthyridine Toll-like Receptor 7 Agonists for Adsorption to Aluminum Hydroxide.
- Author
-
Cortez, Alex, Yongkai Li, Miller, Andrew T., Xiaoyue Zhang, Yue, Kathy, Maginnis, Jillian, Hampton, Janice, Hall, De Shon, Shapiro, Michael, Nayak, Bishnu, D'Oro, Ugo, Chun Li, Skibinski, David, Mbow, M. Lamine, Singh, Manmohan, O'Hagan, Derek T., Cooke, Michael P., Valiante, Nicholas M., and Wu, Tom Y.-H.
- Subjects
- *
TOLL-like receptors , *PHOSPHONATES , *BENZONAPHTHYRIDINE , *ALUMINUM hydroxide , *IMMUNOLOGICAL adjuvants , *THERAPEUTICS - Abstract
Small molecule Toll-like receptor 7 (TLR7) agonists have been used as vaccine adjuvants by enhancing innate immune activation to afford better adaptive response. Localized TLR7 agonists without systemic exposure can afford good adjuvanticity, suggesting peripheral innate activation (non-antigen-specific) is not required for immune priming. To enhance colocalization of antigen and adjuvant, benzonaphthyridine (BZN) TLR7 agonists are chemically modified with phosphonates to allow adsorption onto aluminum hydroxide (alum), a formulation commonly used in vaccines for antigen stabilization and injection site deposition. The adsorption process is facilitated by enhancing aqueous solubility of BZN analogs to avoid physical mixture of two insoluble particulates. These BZN-phosphonates are highly adsorbed onto alum, which significantly reduced systemic exposure and increased local retention post injection. This report demonstrates a novel approach in vaccine adjuvant design using phosphonate modification to afford adsorption of small molecule immune potentiator (SMIP) onto alum, thereby enhancing co-delivery with antigen. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
7. Antimalarial Activity of 4-Amidinoquinoline and 10-Amidinobenzonaphthyridine Derivatives.
- Author
-
Korotchenko, Vasiliy, Sathunuru, Ramadas, Gerena, Lucia, Caridha, Diana, Qigui Li, Kreishman-Deitrick, Mara, Smith, Philip L., and Lin, Ai J.
- Subjects
- *
ANTIMALARIALS , *QUINOLINE , *BENZONAPHTHYRIDINE , *CHEMICAL derivatives , *DRUG resistance in microorganisms - Abstract
Chloroquine (CQ) has been used as first line malaria therapeutic drug for decades. Emergence of CQ drug-resistant Plasmodium falciparum malaria throughout endemic areas of the world has limited its clinical value. Mefloquine (MQ) has been used as an effective malaria prophylactic drug due to its being long-acting and having a high potency against blood stage P. falciparum (Pf). However, serious CNS toxicity of MQ has compromised its clinical value as a prophylaxis drug. Therefore, new and inexpensive antimalarial drugs with no cross-resistance to CQ or CNS toxicity are urgently needed to combat this deadly human disease. In this study, a series of new 4-amidinoquinoline (4-AMQ) and 10-amidinobenzonaphthyridine (10-AMB) derivatives were designed, prepared, and assessed to search for new therapeutic agents to replace CQ and MQ. The new derivatives displayed high activity in vitro and in vivo, with no cross-resistance to CQ, and none were toxic in mice up to 160 mpk × 3. The best compound shows IC50 < 1 ng/mL against D6, W2 and C235 Pf clones, low inhibitory activity in hERG K+ channel blockage testing, negativity in the Ames test, and 5/5 cure @ <15 mpk × 3 in mice infected with Plasmodium berghei. In addition to these desirable pharmacological profiles, compound 13b, one of the most active compounds, is metabolically stable in both human and mouse liver microsomal preparations and has a plasma t1/2 of 50 h in mice, which made it a good MQ replacement candidate. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
8. Iron(III) Chloride Catalyzed Synthesis of Highly Substituted Indolyl-Tetrahydroquinoline Derivatives by Using Indolylnitroalkene as Dienophiles and Its Application to the Synthesis of Indolo-Benzonaphthyridine Derivatives.
- Author
-
Zanwar, Manoj R., Gawande, Sachin D., Kavala, Veerababurao, Kuo, Chun ‐ Wei, and Yao, Ching ‐ Fa
- Subjects
- *
CHEMICAL synthesis , *BENZONAPHTHYRIDINE , *POLYCYCLIC compounds , *DIENOPHILES , *DIELS-Alder reaction - Abstract
An efficient iron(III) chloride catalyzed synthesis of highly substituted indolyltetrahydroquinoline derivatives from easily available starting materials, including indolylnitroalkenes, substituted anilines and various aldehydes is reported. The reaction utilized strong electron deficient dienophiles like indolylnitroalkene via a Povarov approach. The methodology shows good functional group tolerance and can be used to prepare fused indolo-benzonaphthyridine derivatives. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
9. Selective cellular uptake and retention of SN 28049, a new DNA-binding topoisomerase II-directed antitumor agent.
- Author
-
Chen, Ying, Lukka, Pradeep, Joseph, Wayne, Finlay, Graeme, Paxton, James, McKeage, Mark, and Baguley, Bruce
- Subjects
- *
DNA-binding proteins , *DNA topoisomerase II , *ANTINEOPLASTIC agents , *LABORATORY mice , *PHARMACOKINETICS , *DOXORUBICIN , *FLUORESCENCE microscopy - Abstract
Purpose: SN 28049 is a new DNA-binding topoisomerase II poison identified by its curative activity against the murine colon 38 carcinoma. Previous studies showed activity to be associated with selective drug accumulation and retention in tumour tissue. Retention varied widely among different tumours and was related to antitumour activity. We determined whether differences in the uptake and retention of SN 28049 could be observed in vitro. Methods: The Co38P and LLTC lines were derived from the murine colon 38 carcinoma and Lewis lung carcinoma (3LL), respectively. The NZM4, NZM10 and NZM52 human melanoma lines, as well as the CCRF/CEM, CEM/VLB100 and CEM/E1000 human leukaemia lines were also utilised. Cell-associated drug was measured by liquid chromatography-mass spectrometry, laser-scanning confocal microscopy and fluorescence microscopy. Data for SN 28049 were compared for four SN 28049 analogues, for the structurally related drug N-[2-(dimethylamino)-ethyl]acridine-4-carboxamide (DACA) and for doxorubicin. Results: Cellular uptake of SN 28049 was rapid and associated with increased fluorescence in cytoplasmic vesicles or bodies. SN 28049 uptake after an incubation time of 1 h varied widely with different cell lines (2-98 pmol/10 cells) and did not correlate with growth inhibitory concentrations (IC values), which also varied widely (1.2-19 nM). Changes in the length of the N-linked side chain of SN 28049 had large effects on drug uptake by Co38P cells. SN 28049 uptake by CCRF/CEM cells was only slightly affected by the expression of P-glycoprotein (CEM/VLB100) or MRP1 protein (CEM/E1000). As measured by cytoplasmic fluorescence, SN 28049 was taken up rapidly and retained strongly by Co38P cells, DACA was taken up rapidly and retained poorly, and doxorubicin was taken up slowly and retained moderately. Conclusions: The results suggest that SN 28049 is actively transported into cytoplasmic vesicles. While vesicle-associated drug is not important for intrinsic cytotoxicity, it may play a key role as a 'slow release' form that modifies pharmacokinetics in multicellular structures such as tumours. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
10. Transformations of 10-Substituted Tetrahydrobenzo[b][1,6]naphthyridines through Interaction with Dehydrobenzene.
- Author
-
Varlamov, A., Guranova, N., Listratova, A., Borisova, T., Khrustalev, V., Titov, A., and Voskressensky, L.
- Subjects
- *
BENZONAPHTHYRIDINE , *DEHYDROARENES , *STEVENS rearrangement , *POLYCYCLIC aromatic compounds , *POLYCYCLIC compounds - Abstract
The regioselectivity of dehydrobenzene reaction with 10-substituted benzo[ b][1,6]naphthyridines was found to depend on electronic effects due to the C-10 substituent. Stevens rearrangement of 10-cyano-substituted naphthyridines produced 1-alkyl-2-phenyltetrahydrobenzonaphthyridines. 10-Carbamoyl-substituted naphthyridines underwent Hoffman cleavage of the tetrahydropyridine ring, giving 3-phenylallylaminomethyl-2-vinylquinolines. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
11. Synthetic Remodeling of the Chartreusin Pathway to Tune Antiproliferative and Antibacterial Activities.
- Author
-
Ueberschaar, Nico, Zhongli Xu, Scherlach, Kirstin, Metsä-Ketelä, Mikko, Bretschneider, Tom, Dahse, Hans-Martin, Görls, Helmar, and Hertweck, Christian
- Subjects
- *
BENZONAPHTHYRIDINE , *POLYKETIDES , *COUMARINS , *ANTIBACTERIAL agents , *AGLYCONES - Abstract
Natural products of the benzonaphthopyranone class, such as chartreusin, elsamicin A, gilvocarcin, and polycarcin, represent potent leads for urgently needed anticancer therapeutics and antibiotics. Since synthetic protocols for altering their architectures are limited, we harnessed enzymatic promiscuity to generate a focused library of chartreusin derivatives. Pathway engineering of the chartreusin polyketide synthase, mutational synthesis, and molecular modeling were employed to successfully tailor the structure of chartreusin. For the synthesis of the aglycones, improved synthetic avenues to substituted coumarin building blocks were established. Using an engineered mutant, in total 11 new chartreusin analogs (desmethyl, methyl, ethyl, vinyl, ethynyl, bromo, hydroxy, methoxy, and corresponding (1→2) abeo-chartreusins) were generated and fully characterized. Their biological evaluation revealed an unexpected impact of the ring substituents on antiproliferative and antibacterial activities. Irradiation of vinyl- and ethynyl-substituted derivatives with blue light resulted in an improved antiproliferative potency against a colorectal cancer cell line. In contrast, the replacement of a methyl group by hydrogen caused a drastically decreased cytotoxicity but markedly enhanced antimycobacterial activity. Furthermore, mutasynthesis of bromochartreusin led to the first crystal structure of a chartreusin derivative that is not modified in the glycoside residue. Beyond showcasing the possibility of converting diverse, fully synthetic polyphenolic aglycones into the corresponding glycosides in a whole-cell approach, this work identified new chartreusins with fine-tuned properties as promising candidates for further development as therapeutics. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
12. Palladium-catalyzed one-pot synthesis of benzo[b][1,6]naphthyridines via Sonogashira coupling and annulation reactions from 2-chloroquinoline-3-carbonitriles.
- Author
-
Singh, Radhey M., Kumar, Ritush, Sharma, Neha, and Asthana, Mrityunjaya
- Subjects
- *
PALLADIUM catalysts , *BENZONAPHTHYRIDINE , *SONOGASHIRA reaction , *ANNULATION , *QUINOLINE , *CHEMICAL synthesis , *NAPHTHYRIDINES - Abstract
Abstract: Palladium-catalyzed one-pot synthesis of 1,3-disubstituted benzo[b][1,6]naphthyridines and [1,6]naphthyridines has been described from easily accessible precursors, 2-chloroquinoline-3-carbonitriles and 2-chloropyrido-3-carbonitrile via sequential additions of palladium-catalyst for Sonogashira-coupling and the following annulations in good to excellent yields. A plausible mechanism for annulation is discussed. [Copyright &y& Elsevier]
- Published
- 2013
- Full Text
- View/download PDF
13. Tumour tissue selectivity in the uptake and retention of SN 28049, a new topoisomerase II-directed anticancer agent.
- Author
-
Lukka, Pradeep, Chen, Ying, Finlay, Graeme, Joseph, Wayne, Richardson, Emma, Paxton, James, and Baguley, Bruce
- Subjects
- *
TUMOR treatment , *TISSUES , *DNA topoisomerase II , *ANTINEOPLASTIC agents , *DOXORUBICIN , *TUMOR growth , *BENZONAPHTHYRIDINE , *CONFOCAL microscopy , *PHARMACOKINETICS - Abstract
Purpose: A variety of anticancer drugs, including doxorubicin and mitoxantrone, have structures in which a DNA-intercalating chromophore is linked to a positively charged side chain. These drugs generally inhibit tumour growth and survival by poisoning the enzyme DNA topoisomerase II. SN 28049, a benzonaphthyridine derivative with these properties, has curative activity against the Colon 38 tumour in mice. Previous pharmacokinetic studies have demonstrated tumour-selective retention with approximately 20-fold higher area under the concentration-time curve (AUC) for tumour tissue as compared to normal tissues. We have investigated here whether such retention is tumour specific. Methods: Plasma and tissue pharmacokinetics were assessed in the murine Lewis lung (LL3) tumour in C57 BL/6 mice and in xenografts of the NZM4, NZM10 and NZM52 human melanoma lines in Balb/c Rag-1 immunodeficient mice. The in vitro cellular localisation of SN 28049 in murine and human cell lines was studied by confocal fluorescence microscopy. Results: A 260-fold variation, from 8.9 μM h (NZM4) to 2,334 μM h (Colon 38), was found among the different tumours. Only small variations were observed in the corresponding plasma AUC (2.9-5 μM h). Moreover, in vivo activity, as measured by tumour growth delay, varied from 1 day (NZM4) to curative (Colon 38), consistent with the tumour pharmacokinetic data. In cultured cell lines, SN 28049 was found in cytoplasmic bodies, suggesting that drug sequestration could contribute to tumour pharmacokinetics. Conclusion: SN 28049 shows dramatic differences in both tumour AUC and antitumour activity against different tumours. These differences point to the presence of a tumour-specific uptake and retention mechanism. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
14. Effect of Substituents in the Syntheses of Phenyl-Substituted Dibenzonaphthyridines.
- Author
-
Manoj, Manickam and Prasad, Karnam Jayaramapillai Rajendra
- Subjects
- *
SUBSTITUENTS (Chemistry) , *CHEMICAL synthesis , *BENZONAPHTHYRIDINE , *AMINODIPHENYLAMINE , *PYRIDINE derivatives , *TEMPERATURE - Abstract
A facile and elegant syntheses of linear and angular phenyl-substituted dibenzonaphthyridines from 2,4-dichloroquinolines through anilinoquinolines have been developed. The substituents in the 4th position of the anilinoquinoline and the temperature were found to play a vital role in the regulation of the yield towards the synthesis of the final compounds. The methyl group in the 7th position of the naphthyridin-11-ones was found to hinder the N-methylation reaction sterically, consequently increasing the reaction time than other derivatives. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
15. Efficient synthesis of novel benzo[b][1,8]naphthyridin-4(1H)-ones and pyrido[2,3-b]quinoxalin-4(1H)-ones from alkynones and primary amines
- Author
-
Iaroshenko, Viktor O., Zahid, Muhammad, Mkrtchyan, Satenik, Gevorgyan, Ashot, Altenburger, Kai, Knepper, Ingo, Villinger, Alexander, Sosnovskikh, Vyacheslav Ya., and Langer, Peter
- Subjects
- *
ORGANIC synthesis , *BENZONAPHTHYRIDINE , *QUINOXALINE compounds , *AMINES , *PALLADIUM catalysts , *RING formation (Chemistry) - Abstract
Abstract: An efficient palladium-catalyzed cyclization of o-chlorohetaryl ynones with aliphatic and aromatic primary amines represents a simple access to a wide range of benzo[b][1,8]naphthyridin-4(1H)-one and pyrido[2,3-b]quinoxalin-4(1H)-one derivatives in good to excellent yields. [Copyright &y& Elsevier]
- Published
- 2013
- Full Text
- View/download PDF
16. First total synthesis and determination of the absolute configuration of 1-N-methyl-3-methylamino-[N-butanoicacid-3-(9-methyl-8-propen-7-one)-amide]-benzo[f][1,7]naphthyridine-2-one, a novel benzonaphthyridine alkaloid
- Author
-
Tian, Chengsen, Jiao, Xiaozhen, Liu, Xiaoyu, Li, Renze, Dong, Liang, Liu, Xiaojin, Zhang, Zhigang, Xu, Jun, Xu, Minjuan, and Xie, Ping
- Subjects
- *
AMIDES , *ORGANIC synthesis , *NAPHTHYRIDINES , *BENZONAPHTHYRIDINE , *ALKALOIDS , *KETONES , *MOLECULAR structure , *GLUTAMIC acid , *CHEMICAL reactions - Abstract
Abstract: The first total synthesis of benzonaphthyridine alkaloid (1), a unique diazaphenathrene alkaloid isolated from mangrove-derived Streptomyces albogriseolus, was accomplished. The core structure was unequivocally constructed via several key transformations, such as Knoevenagel condensation, Curtius rearrangement, and cyclic carbamate formation–reduction sequence. The chiral unsaturated ketone acid moiety was synthesized from N-tert-butoxycarbonyl-l-glutamic acid gamma-tert-butyl ester (15). The absolute configuration was determined. [Copyright &y& Elsevier]
- Published
- 2012
- Full Text
- View/download PDF
17. Comparison of a homologous series of benzonaphthyridine anti-cancer agents in mice: divergence between tumour and plasma pharmacokinetics.
- Author
-
Lukka, Pradeep, Paxton, James, Kestell, Philip, and Baguley, Bruce
- Subjects
- *
COLON cancer treatment , *BENZONAPHTHYRIDINE , *ANTINEOPLASTIC agents , *LABORATORY mice , *PHARMACOKINETICS , *NAPHTHYRIDINES , *CARBOXAMIDES - Abstract
Purpose: N-[2-(dimethylamino)ethyl]-2,6-dimethyl-1-oxo-1,2-dihydrobenzo[b]-1,6-naphthyridine-4-carboxamide (SN 28049), a DNA-binding benzonaphthyridine, has shown curative activity against colon-38 adenocarcinoma after a single dose in mice. A homologous series of 5 compounds, where the 2-methyl group was replaced by a hydrogen, ethyl, propyl, or butyl, was used to evaluate the role of lipophilicity and tumour pharmacokinetics on their antitumour activity. Methods: All analogues were administered (25 μmol/kg) to healthy and tumour-bearing C57 Bl/6 mice and concentrations were measured in plasma, brain, heart, kidney, liver, lung, and tumour tissues. Microsomal stability studies were performed with mouse livers and plasma protein binding studies by equilibrium dialysis. Results: Plasma pharmacokinetics conformed to a model where increasing lipophilicity was associated with a decreasing area under the concentration-time curve (AUC), an increasing clearance and volume of distribution. In contrast, tumour pharmacokinetic parameters showed a very different relationship, where the AUC of the methyl derivative (2,334 μM h) was 89-fold higher than that of the hydrogen derivative (26.3 μM h), with other homologues having intermediate values. The tumour AUC correlated ( r = −0.98, P = 2 × 10) with the in vivo antitumour activity of this series. The methyl derivative had a 22 min microsomal half-life, while other analogues ranged from 1.6 to 12.2 min. The plasma-free fraction decreased (17-5 %) significantly with lipophilicity ( r = 0.96, P = 2 × 10). Conclusion: The plasma pharmacokinetics of this series is related to changes in drug lipophilicity. However, the tumour pharmacokinetics reveals a strong dependence on the nitrogen substituent on the benzonaphthyridine chromophore, with the methyl group providing by far the best tumour tissue retention. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
18. Oxidative stress and cell-cycle change induced by coexposed PCB126 and benzo(a) pyrene to human hepatoma (HepG2) cells.
- Author
-
Wei, Wei, Li, Xiao-Feng, Li, Xiao-Nuan, Chen, Xue-Min, Liu, Ai-Lin, and Lu, Wen-Qing
- Subjects
OXIDATIVE stress ,BENZONAPHTHYRIDINE ,CELL cycle ,HEPATOCELLULAR carcinoma ,POLYCHLORINATED biphenyls ,GENETIC toxicology - Abstract
Benzo(a)pyrene (BaP) never exists in the environment as a single compound but always coexists with other chemicals. These chemicals may affect the toxicity of BaP. Our previous study confirmed that polychlorinated biphenyls (PCBs), which were recently found coexisting with BaP in various environmental media, dramatically enhanced the genotoxicity of BaP. But the known mechanisms associated with this phenomenon are limited. Because BaP's genotoxicity is highly associated with its ability to induce the oxidative stress, we propose that the coexistence of PCBs may enhance BaP's genotoxicity by affecting BaP-induced oxidative stress. In this study, the HepG2 cells were treated with either BaP (50 μM), 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) (0.01, 0.1, 1, and 10 nM), or pretreated with PCB126 followed by a coexposure to BaP and PCB126. We found that the exposure to BaP alone effectively increased the level of reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), and the percentage of cells in G0/G1 phase, but decreased the percentage of S-phase cells. Compared to BaP alone, coexposure to both BaP and PCB126 effectively enhanced the levels of ROS and MDA as well as the percentage of cells in S phase, but decreased the levels of GSH and percentage of cells in G0/ G1 phase. Our findings suggest that increasing oxidative stress and impairing the normal cell-cycle control may be mechanisms by which PCB126 enhances the genotoxity of BaP exposure. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
19. A rapid LC–MS/MS method for the quantitation of a series of benzonaphthyridine derivatives: Application to in vivo pharmacokinetic and lipophilicity studies in drug development
- Author
-
Lukka, Pradeep B., Paxton, James W., Atwell, Graham J., Kestell, Philip, and Baguley, Bruce C.
- Subjects
- *
BENZONAPHTHYRIDINE , *ORGANIC compounds , *DRUG derivatives , *DRUG lipophilicity , *DRUG development , *PHARMACOKINETICS , *LIQUID chromatography-mass spectrometry , *QUANTITATIVE research , *THERAPEUTICS - Abstract
Abstract: Drug lipophilicity is a vital physicochemical parameter that influences drug absorption, distribution, metabolism, excretion and toxicology. A comparative study of a homologous series based on a pharmaceutically active drug represents a powerful approach to the study of the effects of drug lipophilicity. We have developed a rapid and sensitive LC–MS/MS method suitable for such a homologous series and applied it to a series of DNA binding benzonaphthyridine-based antitumour drugs of differing lipophilicity. The method used a gradient elution with a run time of 7min for simultaneous quantitation of five analogues in a pooled sample. Method validation was carried out in plasma (human and mouse) and mouse tissues (brain, heart, kidney, liver and lung). It had a limit of quantitation of 0.001μmol/L and was linear (0.001–0.3μmol/L) in all matrices with acceptable intra- and inter-assay precision and accuracy. This method allowed the pharmacokinetic parameters of these compounds in mice to be related to their lipophilicity as determined by their partition coefficient (Log D). Both the plasma CL (r =0.95; P =2×10−7) and V ss (r =0.95; P =2×10−7) exhibited a significant positive correlation with Log D values after intravenous bolus administration to mice. Consequently the plasma mean residence time for each of these five analogues decreased with increasing lipophilicity. There was also a significant positive correlation (r =0.91; P =2×10−7) between Log D values and the brain to plasma AUC ratio indicating the importance of lipophilicity in the distribution of these compounds into the brain tissue. [Copyright &y& Elsevier]
- Published
- 2012
- Full Text
- View/download PDF
20. Low incidence of long-term respiratory impairment in Hodgkin lymphoma survivors.
- Author
-
Avivi, Irit, Hardak, Emilia, Shaham, Beatrice, Igla, Mordechai, Rowe, Jacob, and Dann, Eldad
- Subjects
- *
POLYCYCLIC compounds , *BENZONAPHTHYRIDINE , *HODGKIN'S disease , *ANTINEOPLASTIC agents , *DRUG therapy , *ANTINEOPLASTIC antibiotics - Abstract
Introduction of new chemotherapy regimens over the last decade resulted in 90% survival in patients with Hodgkin lymphoma (HL), which enhances significance of abrogating chemotherapy-related long-term toxicities in young subjects. The present trial evaluated incidence of long-term respiratory complications associated with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) or bleomycin sulfate, etoposide phosphate, doxorubicin hydrochloride (Adriamycin), cyclophosphamide, vincristine sulfate (Oncovin), procarbazine hydrochloride, and prednisone (BEACOPP). Sixty-seven HL patients, 21 treated with ABVD and 46 with BEACOPP, underwent prospective respiratory evaluation. Median follow-up from chemotherapy completion to respiratory assessment was 61 months. Abnormal lung function tests (LFT) were found in nine patients (13.6%)-three with functional dyspnea and six asymptomatic-with reduced DLCO (≤70%), VC, and TLC. Previous history of bleomycin pulmonary toxicity was found to be the only statistically significant factor for chronic respiratory impairment (75% vs. 10%, p = 0.007, relative risk (RR) = 28; 95% CI, 2.5-313). However, abnormal LFT tended to occur more frequently in patients receiving mantle field irradiation (18% vs. 9%, RR = 2.2), those who experienced respiratory infection (25% vs. 13%, RR = 2.25), and patients treated with ABVD compared to BEACOPP (19% vs. 11%, RR = 1.9). Long-term respiratory impairment in HL survivors is unusual and rarely results in functional discomfort. BEACOPP is 'respiratory safe,' being associated with a nonsignificant risk for long-term respiratory dysfunction. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
21. Antiproliferative Effect of Aaptamine on Human Chronic Myeloid Leukemia K562 Cells.
- Author
-
Meihua Jin, Wennan Zhao, Yanwen Zhang, Kobayashi, Motomasa, Hongquan Duan, and Dexin Kong
- Subjects
- *
CELLULAR pathology , *CANCER cells , *LEUKEMIA , *SPONGES (Invertebrates) , *POLYCYCLIC compounds , *BENZONAPHTHYRIDINE , *ALKALOIDS - Abstract
We previously isolated aaptamine, a benzonaphthyridine alkaloid, from marine sponge Aaptos suberitoids. In this study, we investigated the anti-proliferative effect of aaptamine on chronic myeloid leukemia (CML) K562 cells. Aaptamine inhibited growth of K562 with a GI50 as 10 µM, and arrested cell cycle at G2/M phase. Western blot analysis indicated that aaptamine induced p21 expression in K562 cells. Moreover, p21 promoter was activated by aaptamine treatment in p21 transfected K562 cells. Since K562 is p53 negative, aaptamine was demonstrated to be a p53-independent p21 inducer in CML cells. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
22. Friedlander Synthesis of Benzo[h]naphthyridines from o -Aminoaldehydes.
- Author
-
Rote, Ramhari V., Shelar, Deepak P., Patil, Sandeep R., and Jachak, Madhukar N.
- Subjects
- *
CHEMICAL reactions , *QUINOLINE , *BENZONAPHTHYRIDINE , *CONDENSATION , *CARBENES , *AMINO acids , *SOLVENTS , *ORGANIC compounds research , *CHEMICAL processes - Abstract
The article focuses on the applications and description of the Friedlander reaction method. It says that Friedlander reaction is one of the simplest methods for the synthesis of several derivatives including quinoline, pyrazolopyridine, and benzonaphthyridine. It states that Friedlander condensation of 4-amino-6-chloroquinoline-3-carbalde hyde (1) with several reactive methylene compounds was made under varied reaction conditions. It mentions that the Friedlander condensation of 1 with reaction methylene compounds done by neat heating gives a green method, even though in low yields, since the said method does not need solvent and requires simple work-up.
- Published
- 2011
- Full Text
- View/download PDF
23. A convenient route to cyano derivatives of benzonaphthyridines.
- Author
-
Bachowska, B.
- Subjects
- *
BENZONAPHTHYRIDINE , *NITROGEN oxides , *NITRILES , *ALKALIES , *HETEROCYCLIC compounds - Abstract
A smooth synthesis of benzo[c][1,5]naphthyridine-6-carbonitrile and benzo[h][1,6]naphthyridine-5-carbonitrile, starting from benzonaphthyridine N-oxides, is achieved by treatment with trimethylsilane carbonitrile (Me3SiCN) in CH2Cl2 at 0-5 °C. The resulting nitriles are then hydrolyzed to the corresponding acids by boiling in aqueous alkali. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
24. Synthesis and Anti-Intestinal Nematode Activity of Variously Substituted Benzonaphthyridine Derivatives.
- Author
-
Li-Ping Duan, Ai-Dan Wen, Ning-Bo Wu, Yi Tao, and Hao-Bing Zhang
- Subjects
- *
NEMATODE infections , *LABORATORY rats , *PARASITES , *BENZONAPHTHYRIDINE , *AMINO acids - Abstract
A series of benzonaphthyridine derivatives bearing the C=N linkage moiety were designed and synthesized. The structures of all the newly synthesized compounds were identified by elemental analysis, 1H-NMR, 13C-NMR and MS. Their anti-intestinal nematode activities against Nippostrongylus brazilliensis were evaluated in vivo by an oral route in male rats. Among these compounds, at concentrations of 10 mg/kg of rat, the compound 7-chloro-2-methoxy-10-(4-(4′-(1H-indol-5′-yl)methylene)aminophenyl)-amino-benzo[b][1,5] naphthyridine (4n) produced the highest activity, with 80.2% deparasitization. These compounds may find usefulness in the discovery and development of new anti-intestinal drugs. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
25. Pharmacokinetics and distribution of SN 28049, a novel DNA binding anticancer agent, in mice.
- Author
-
Lukka, Pradeep B., Paxton, James W., Kestell, Philip, and Baguley, Bruce C.
- Subjects
- *
DNA topoisomerase II , *ANTINEOPLASTIC agents , *PHARMACOKINETICS , *MICE , *NAPHTHYRIDINES - Abstract
N-[2-(Dimethylamino)ethyl]-2,6-dimethyl-1-oxo-1,2-dihydrobenzo[b]-1,6-naphthyridine-4-carboxamide (SN 28049) is a potent DNA binding topoisomerase II poison that shows excellent antitumour activity in a colon-38 murine tumour model in comparison to standard topoisomerase II poisons. We report here the preclinical pharmacokinetics of SN 28049. C57 Bl/6 mice ( n = 3 per time point) were treated with a single i.v., i.p. or p.o. administration (8.9 mg/kg). Plasma and tissue samples were analysed using a validated LC/MS method utilizing a homologue as an internal standard. The assay range was 0.062–2.5 μM with a quantitation limit of 0.062 μM and a detection limit of 0.025 μM. Acceptable intra- and inter-assay accuracy (95–105%) and precision (<6.5% RSD) were achieved. Following i.v. administration, SN 28049 demonstrated 2-compartment model kinetics with a volume of distribution of 42.3 ± 4.1 l/kg, a plasma clearance of 12.1 ± 0.5 l/h per kg and distribution and elimination half-lives of 0.15 ± 0.02 and 2.8 ± 0.2 h (mean ± SE), respectively. For all administration routes, SN 28049 concentrations in normal tissues (brain, heart, liver, lung, and kidney) were 12- to 120-fold higher than those in plasma, but half-lives and mean residence times were similar. The i.p. and p.o. bioavailabilities were 83.1 ± 1.5 and 54.5 ± 1.1%, respectively. In the tumour tissue, elimination half-life (9.1 ± 0.7 h) and the mean residence time (18.2 ± 0.7 h) were significantly ( P < 0.001) longer than those of plasma and normal tissues. The tumour area under the concentration–time curve (AUC) (1,316 ± 66 μM h) was also 693-fold greater than the plasma AUC, and considerably higher (~5-fold) than any other tissue examined, indicating selective uptake and retention of SN 28049 in the tumour. We conclude that SN 28049’s high tumour exposure and long tumour retention time is likely to contribute to its high antitumour activity in vivo. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
26. Catenanes and threaded systems: from solution to surfacesDedicated to Professor Jean-Pierre Sauvage on the occasion of his 65th birthday.
- Author
-
Eugenio Coronado, Pablo Gaviña, and Sergio Tatay
- Subjects
- *
POLYCYCLIC compounds , *ACETYLAMINOFLUORENE , *ANTHRACYCLINES , *BENZONAPHTHYRIDINE - Abstract
Functional catenanes and threaded systems able to perform controllable mechanical motions are ideally suited for the design of molecular devices displaying mechanical, electronic, information or sensing functions. These systems have been extensively studied in solution phase and numerous examples of stimuli-driven molecular shuttles have been reported. However, for fully developing their potential applications, they must be interfaced with the macroscopic world. To achieve this objective, in the last few years catenanes and rotaxanes have been organized over surfaces in the form of chemisorbed monolayers or physisorbed monolayers, multilayers and thin films. This tutorial reviewsummarizes the different techniques for the deposition on surfaces and characterization of switchable catenanes and rotaxanes, and highlights the properties of these new functional surfaces and their potential applications. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
27. Sulfate anion templation of macrocycles, capsules, interpenetrated and interlocked structuresDedicated to Prof. Jean-Pierre Sauvage on the occasion of his 65th birthday.
- Author
-
Kathleen M. Mullen and Paul D. Beer
- Subjects
- *
POLYCYCLIC compounds , *ACETYLAMINOFLUORENE , *ANTHRACYCLINES , *BENZONAPHTHYRIDINE - Abstract
This tutorial reviewexamines the potential of anions, in particular sulfate, to template the formation of complex molecular architectures. Until recently, sulfate has been largely overlooked in this area and the examples described herein demonstrate this anion’s versatility in templating the formation of a diverse range of molecular systems including macrocycles, helixes, molecular capsules, interpenetrated and interlocked assemblies such as catenanes. In addition sulfate has been shown to template the formation of interpenetrated structures on a range of surfaces including gold, polystyrene beads and silicate nanoparticles, highlighting the potential of this anion in the fabrication of functional sensory devices exhibiting highly selective binding behaviour. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
28. Topology in molecules inspired, seen and representedDedicated to Professor Jean-Pierre Sauvage on the occasion of his 65th birthday.
- Author
-
David B. Amabilino and Lluïsa Pérez-García
- Subjects
- *
POLYCYCLIC compounds , *ACETYLAMINOFLUORENE , *ANTHRACYCLINES , *BENZONAPHTHYRIDINE - Abstract
The way in which molecules are imagined and subsequently represented in drawings or models is a fundamental part of the chemist’s activity. In this tutorial reviewwe shall discuss these doings for molecules which contain an element of entanglement and whose structural representation on a plane requires the presence of crossing points. The review provides a personal view of finding inspiration, how to draw and understand topologically complex molecules, and the way they can be “switched”. The review compares and contrasts approaches to illustration and conception of catenanes and knots and the dynamic processes taking place within them, and discusses the graphic tools used to portray them. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
29. Ravels: knot-free but not free. Novel entanglements of graphs in 3-space.
- Author
-
Toen Castle, Myfanwy E. Evans, and S. T. Hyde
- Subjects
- *
POLYCYCLIC compounds , *ACETYLAMINOFLUORENE , *ANTHRACYCLINES , *BENZONAPHTHYRIDINE - Abstract
Molecular and extended framework materials, from proteins to catenanes and metal–organic frameworks, can assume knotted configurations in their bonding networks (the chemical graph). Indeed, knot theory and structural chemistry have remained closely allied, due to those connections. Here we introduce a new class of graph entanglement: “ravels”. These ravels—often chiral—tangle a graph without the presence of knots. Just as knots lie within cycles in the graph, ravels lie in the vicinity of a vertex. We introduce various species of ravels, including fragile ravels, composite ravels and shelled ravels. The role of ravels is examined in the context of finite and infinite graphs—analogous to molecular and extended framework nets—related to the diamond net. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
30. Competitive formation of condensed azines and dihydropyridines in the reaction of ethyl 3,3-diaminoacrylate with o-halo carbaldehydes.
- Author
-
Eliseev, I., Dar’in, D., Selivanov, S., Lobanov, P., and Potekhin, A.
- Subjects
- *
DIHYDROPYRIDINE , *PYRIDINE , *QUINOLINE , *ORGANIC compounds , *AMLODIPINE - Abstract
The reaction of ethyl 3,3-diaminoacrylate with quinoline-3-carbaldehydes and 3-nitrobenzaldehydes to give a dihydropyridine and condensed azine has been studied with respect to the number and reactivity of the halogen atoms in an ortho position to the formyl groups. For the series of quinoline-3-carbaldehydes it was found that the reaction course is determined by the number of chlorine atoms. 2-and 4-Chloroquinoline-3-carbaldehydes give dihydropyridines and a benzo[c][2,7-]naphthyridine is formed in the reaction with 2,4-dichloroquinoline-3-carbaldehyde. The main products in the case of nitrobenzaldehydes are dihydropyridines which points the deciding influence of the low electrophilicity of aromatic ring. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
31. Three-Component One-Pot Synthesis of Novel Benzo[b] 1,8-naphthyridines Catalyzed by Bismuth(III) Chloride.
- Author
-
Ravikumar Naik, Tangali R., Bhojya Naik, Halehatty S., Prakasha Naik, Halehatty R., and Bindu, P. J.
- Subjects
- *
PHYSICAL & theoretical chemistry , *POLYCYCLIC compounds , *ALDEHYDES , *BENZONAPHTHYRIDINE , *ORGANIC compounds , *CHLORIDES , *CHEMICAL reactions , *NAPHTHYRIDINES , *HETEROCYCLIC compounds - Abstract
Anovel and efficient three-component one-pot synthesis of benzo[b]1,8-naphthyridines by 2-amino-4-methylquinoline, aromatic aldehydes, and malononitrile was done. The reaction was catalyzed by an acidic Bismuth(III) chloride, functionalized Bismuth(III) chloride, at room temperature to give various benzo[b]1,8-naphthyridines in high yields. The Bismuth(III) chloride is an environmentally friendly catalyst. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
32. Pyridinium N-2′-pyridylaminide: radical cyclization for the synthesis of benzonaphthyridine derivatives
- Author
-
Núñez, Araceli, Sánchez, Aránzazu, Burgos, Carolina, and Alvarez-Builla, Julio
- Subjects
- *
BENZONAPHTHYRIDINE , *POLYCYCLIC compounds , *ASYMMETRIC synthesis , *RING formation (Chemistry) - Abstract
Abstract: The synthesis of benzonaphthyridine derivatives that incorporate a 2-aminopyridine moiety can be performed by intramolecular radical pyridylation of the appropriate substrates, obtained from pyridinium N-2′-pyridylaminide, using TTMSS and AIBN. [Copyright &y& Elsevier]
- Published
- 2007
- Full Text
- View/download PDF
33. 4-hydroxy-2-quinolones. 114. Synthesis and structure of 6-R-5-hydroxy-2,4-dioxo-2,3,4,6-tetrahydrobenzo-[ c][2,7]naphthyridine-1-carbonitriles.
- Author
-
Ukrainets, I. V., Bereznyakova, N. L., Parshikov, V. A., and Shishkina, S. V.
- Subjects
- *
HETEROCYCLIC compounds , *HETEROCYCLIC chemistry , *ORGANIC chemistry , *CHEMICAL structure , *NITRILES , *HYDRATION - Abstract
Hydration of ethyl 1-R-4-dicyanomethyl-2-oxo-1,2-dihydroquinoline-3-carboxylate gives the corresponding substituted cyanoacetamides which are readily and quantitatively cyclized to 6-R-5-hydroxy-2,4-dioxo-2,3,4,6-tetrahydrobenzo[c][2,7]naphthyridine-1-carbonitriles in the presence of aqueous base. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
34. Aaptamine, a spongean alkaloid, activates p21 promoter in a p53-independent manner
- Author
-
Aoki, Shunji, Kong, Dexin, Suna, Hideaki, Sowa, Yoshihiro, Sakai, Toshiyuki, Setiawan, Andi, and Kobayashi, Motomasa
- Subjects
- *
BENZONAPHTHYRIDINE , *POLYCYCLIC compounds , *BIOLOGICAL assay , *MESSENGER RNA , *CYTOLOGICAL research - Abstract
Abstract: Aaptamine, a benzonaphthyridine alkaloid was isolated from a marine sponge on the guidance of a bioassay using the transfected human osteosarcoma MG63 cells (MG63luc+). Aaptamine activated p21 promoter stably transfected in MG63 cells dose-dependently at the concentrations of 20–50μM. Expression of p21 and its mRNA in the wild-type MG63 cells also increased by aaptamine-treatment. Furthermore, the cell cycle of MG63 cells was arrested at the G2/M phase within 48h by the aaptamine-treatment. To analyze a responsive element of p21 promoter in the up-regulation of p21 by aaptamine, MG63 cells were transiently transfected with a series of the deleted or mutated promoter segments, and induction of luciferase with aaptamine treatment was examined by using these corresponding transfected cells. The activation of p21 promoter by aaptamine was led through acting Sp1 sites between −82 and −50bp in a p53-independent manner. [Copyright &y& Elsevier]
- Published
- 2006
- Full Text
- View/download PDF
35. Simulation of IR and Raman spectra based on scaled DFT force fields: a case study of 2-(methylthio)benzonitrile, with emphasis on band assignment
- Author
-
Krishnakumar, V., Keresztury, Gábor, Sundius, Tom, and Ramasamy, R.
- Subjects
- *
RAMAN effect , *POLYCYCLIC compounds , *BENZONAPHTHYRIDINE , *FLUIDS - Abstract
The solid phase FT-IR and FT-Raman, solution phase linear dichroism IR (in nematic liquid crystal), and vapor phase GC/IR spectra of 2-(methylthio)benzonitrile have been recorded in the regions 4000–50, 3500–100, 4000–400, and 4000–650 cm-1, respectively. The spectra were interpreted with the aid of normal coordinate analysis following full structure optimizations and force field calculations based on density functional theory (DFT) using standard B3LYP/6-31G* and B3LYP/6-311+G** method and basis set combinations. Normal coordinate calculations were performed with the DFT force field corrected by a recommended set of scaling factors yielding fairly good agreement between observed and calculated frequencies. IR dichroism data revealed an error in band assignment associated with a
ν CS vibration, which could be eliminated only by introducing independent scaling factors for sulfur, whereas the overall frequency fit was further improved. Simulation of infrared and Raman spectra utilizing the results of these calculations led to excellent overall agreement with the observed spectral patterns, especially with the higher level basis set. The SQM approach applying selective scaling of the DFT force field was shown to be superior to the uniform scaling method in its ability to allow for making modifications in the band assignment, resulting in more accurate simulation of IR and Raman spectra including band polarizations and intensity patterns. [Copyright &y& Elsevier]- Published
- 2004
- Full Text
- View/download PDF
36. Comparison of hematin-targeting properties of pynacrine, an acridine analog of the benzonaphthyridine antimalarial pyronaridine.
- Author
-
Sereekhajornjaru, Narumon, Somboon, Chanat, Rattanajak, Roonglawan, Denny, William A., Wilairat, Prapin, and Auparakkitanon, Saranya
- Subjects
- *
HEME , *ACRIDINE , *BENZONAPHTHYRIDINE , *ANTIMALARIALS , *GLUTATHIONE , *PLASMODIUM falciparum , *COMPARATIVE studies - Abstract
The hematin-targeting properties of pynacrine, an acridine analog of the schizontocidal antimalarial drug, pyronaridine, were evaluated to probe the role of the latter's benzonaphthyridine moiety. Pynacrine was as active as pyronaridine in inhibiting glutathione-induced hematin degradation and in enhancing hematin-mediated membrane lysis. It formed a 1:2 complex with hematin but was 50-fold less effective in inhibiting β-hematin formation. However, pynacrine was as potent as pyronaridine in inhibiting intra-erythrocytic Plasmodium falciparum growth in culture, suggesting that it has other off-target(s) effects. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
37. Synthesis and Anti-Intestinal Nematode Activity of Variously Substituted Benzonaphthyridine Derivatives
- Author
-
Ning-Bo Wu, Hao-Bing Zhang, Ai-Dan Wen, Liping Duan, and Yi Tao
- Subjects
Male ,Stereochemistry ,Pharmaceutical Science ,Nippostrongylus brazilliensis ,Mass Spectrometry ,Article ,Analytical Chemistry ,lcsh:QD241-441 ,Antimalarials ,chemistry.chemical_compound ,lcsh:Organic chemistry ,In vivo ,Drug Discovery ,Male rats ,Oral route ,Animals ,Humans ,Moiety ,Nippostrongylus ,Naphthyridines ,Physical and Theoretical Chemistry ,Methylene ,Nuclear Magnetic Resonance, Biomolecular ,Molecular Structure ,biology ,Chemistry ,Antinematodal Agents ,Organic Chemistry ,biology.organism_classification ,C=N linkage ,Rats ,Intestines ,Nematode ,Chemistry (miscellaneous) ,Molecular Medicine ,benzonaphthyridine ,Intestinal nematode - Abstract
A series of benzonaphthyridine derivatives bearing the C=N linkage moiety were designed and synthesized. The structures of all the newly synthesized compounds were identified by elemental analysis, 1 H-NMR, 13 C-NMR and MS. Their anti-intestinal nematode activities against Nippostrongylus brazilliensis were evaluated in vivo by an oral route in male rats. Among these compounds, at concentrations of 10 mg/kg of rat, the compound 7-chloro-2-methoxy-10-(4-(4'-(1H-indol-5'-yl)methylene)aminophenyl)- amino-benzo(b)(1,5) naphthyridine (4n) produced the highest activity, with 80.2% deparasitization. These compounds may find usefulness in the discovery and development of new anti-intestinal drugs.
- Published
- 2011
- Full Text
- View/download PDF
38. ChemInform Abstract: Dibenzonaphthyridinones: Heterocycle-to-Heterocycle Synthetic Strategies and Photophysical Studies.
- Author
-
Palazzo, Teresa A., Patra, Digambara, Yang, Joung S., El Khoury, Elsy, Appleton, Mackenzie G., Haddadin, Makhluf J., Tantillo, Dean J., and Kurth, Mark J.
- Subjects
- *
BENZONAPHTHYRIDINE , *NITROPHENYL compounds , *OXAZOLES synthesis , *PHOTOLUMINESCENCE , *CHEMINFORMATICS - Abstract
The two-step preparation of dibenzonaphthyridinones via 3,5-bis(2-nitrophenyl)-1,2-oxazoles is described. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
39. ChemInform Abstract: An Efficient Synthesis of Indol-3-yl Benzonaphthyridines via Copper(II) Triflate-Catalyzed Heteroannulation.
- Author
-
Prakash, K. S. and Nagarajan, Rajagopal
- Subjects
- *
BENZONAPHTHYRIDINE , *TRIFLATE compounds , *ANNULATION , *COPPER , *QUINOLINE , *ANILINE , *NUCLEOPHILIC addition (Chemistry) - Abstract
The three component reaction of quinolines (I) or (V) with anilines and indoles involves the initial formation of an imine, copper(II) triflate catalyzed 6-endo-dig type annulation, and nucleophilic addition of indole to give the title species under mild conditions. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.