- Microwave assisted synthesis and antibacterial activity of new quinolone derivatives
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A series of novel 6-fluoro-7-(5-alkyl-1,3,4-thiadiazol/oxadiazol-2-ylsulfanyl)-4-quino-lone-3- carboxylic acids were synthesized using microwave irradiation. The compounds were tested for their in vitro antibacterial activity. All compounds containing the 1,3,4-thiadiazole/oxadiazole moiety at position 7 showed promising antibacterial activity.
- Kidwai, Mazaahir,Misra, Preeti,Kumar, Rajesh,Saxena, Rajendra K.,Gupta, Rani,Bradoo, Sapna
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Read Online
- Microwave activated solid support synthesis of new antibacterial quinolones
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A novel synthesis of 6-fluoro-7-(5-aryl-1,3,4-thiadiazol/oxadiazol-2-yl-sulfanyl)-4-quinolone-3- carboxylic acids from 7-chloro-6-fluoro-4-quinolone-3-carboxylic acid and 5-substituted 1,3,4-thiadiazoles/oxadiazoles on basic alumina under microwave activation is described. All compounds were screened for their in vitro antibacterial activity against B. lichenformis, 2689, K. aerogens 2281, S. typhimurium 2501, E. herbicola 2491, and P. vulgaris 2027 and found to possess activities comparable to that of the standard drug norfloxacin.
- Kidwai, Mazaahir,Misra, Preeti,Dave, Bhavesh,Bhushan, Kumar R.,Saxena, Rajendra K.,Singh, Meena
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Read Online
- NEXT-GENERATION MODULATORS OF STIMULATOR OF INTERFERON GENES (STING)
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The present invention relates to compounds of formula (I) and salts, stereoisomers, tautomers or N-oxides thereof that are useful as modulators of STING (Stimulator of Interferon Genes). The present invention further relates to the compounds of formula (I) for use as a medicament and to a pharmaceutical composition comprising said compounds.
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Page/Page column 72-73
(2020/12/30)
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- Synthesis and biological evaluation of small molecule modulators of CDK8/Cyclin C complex with phenylaminoquinoline scaffold
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Background. CDK8/CycC complex has kinase activity towards the carboxyterminal domain of RNA polymerase II, and contributes to the regulation of transcription via association with the mediator complex. Different human malignancies, mainly colorectal and gastric cancers, were produced as a result of overexpression of CDK8/CycC in the mediator complex. Therefore, CDK8/CycC complex represents as a cancer oncogene and it has become a potential target for developing CDK8/CycC modulators. Methods. A series of nine 4-phenylaminoquinoline scaffold-based compounds 5a-i was synthesized, and biologically evaluated as potential CDK8/CycC complex inhibitors. Results. The scaffold substituent effects on the intrinsic inhibitory activity toward CDK8/CycC complex are addressed trying to present a novel outlook of CDK8/CycC Complex inhibitors with 4-phenylaminoquinoline scaffold in cancer therapy. The secondary benzenesulfonamide analogues proved to be the most potent compounds in suppressing CDK8/CycC enzyme, whereas, their primary benzenesulfonamide analogues showed inferior activity. Moreover, the benzene reversed sulfonamide analogues were totally inactive. Discussion. The titled scaffold showed promising inhibitory activity data and there is a crucial role of un/substituted sulfonamido group for CDK8/CycC complex inhibitory activity. Compound 5d showed submicromolar potency against CDK8/CycC (IC50 = 0.639 μM) and it can be used for further investigations and to design another larger library of phenylaminoquinoline scaffold-based analogues in order to establish detailed SARs.
- Al-Sanea, Mohammad M.
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- 3-(Benzo[: D] thiazol-2-yl)-4-aminoquinoline derivatives as novel scaffold topoisomerase i inhibitor via DNA intercalation: Design, synthesis, and antitumor activities
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Twenty-seven 3-(benzo[d]thiazol-2-yl)-4-aminoquinoline derivatives have been designed and synthesized as topoisomerase I inhibitors. The in vitro anti-proliferation evaluation against four human cancer cell lines (MGC-803, HepG-2, T24, and NCI-H460) and one normal cell line (HL-7702) indicated that most of them exhibited potent cytotoxicity. Among them, 5a was identified as the most promising candidate with a low IC50 value of about 2.20 ± 0.14 and was selected for further exploration. Spectroscopic analyses and agarose-gel electrophoresis assays indicated that 5a could interact with DNA and strongly inhibit topoisomerase I (Topo I). Further screening of the Topo I activity of compounds 5b, 5c, 5e, 5f, 5h, 5i, 5j, 5l, and 5n suggested that some of the compounds might exert quite a different cytotoxicity profile to that of 5a. Molecular modeling studies confirmed that 5a adopts a unique mode to interact with DNA and Topo I. Other molecular mechanistic studies suggested that the treatment of MGC-803 cells with 5a induces S phase arrest, up-regulates the pro-apoptotic protein, down-regulates the anti-apoptotic protein, activates caspase-3, and subsequently induces mitochondrial dysfunction so as to induce cell apoptosis. The in vivo efficiency of 5a was also evaluated on MGC-803 xenograft nude mice and the relative tumor growth inhibition was 42.4percent at 12 mg kg-1 without an obvious loss in the body weight. This journal is
- Chen, Nan-Ying,Gu, Zi-Yu,Li, Xiao-Juan,Liao, Hao-Ran,Mo, Dong-Liang,Pan, Cheng-Xue,Su, Gui-Fa,Yuan, Jing-Mei,Zhang, Guo-Hai
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p. 11203 - 11214
(2020/07/15)
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- Synthesis and biological evaluation of novel 3-(quinolin-4-ylamino)benzenesulfonamidesAQ3 as carbonic anhydrase isoforms I and II inhibitors
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Carbonic anhydrases (CAs, EC 4.2.1.1) are crucial metalloenzymes that are involved in diverse bioprocesses. We report the synthesis and biological evaluation of novel series of benzenesulfonamides incorporating un/substituted ethyl quinoline-3-carboxylate moieties. The newly synthesised compounds were in vitro evaluated as inhibitors of the cytosolic human (h) isoforms hCA I and II. Both isoforms hCA I and II were inhibited by the quinolines reported here in variable degrees: hCA I was inhibited with KIs in the range of 0.966–9.091 μM, whereas hCA II in the range of 0.083–3.594 μM. The primary 7-chloro-6-flouro substituted sulphfonamide derivative 6e (KI = 0.083 μM) proved to be the most active quinoline in inhibiting hCA II, whereas, its secondary sulfonamide analog failed to inhibit the hCA II up to 10 μM, confirming the crucial role of the primary sulphfonamide group, as a zinc-binding group for CA inhibitory activity.
- Al-Sanea, Mohammad M.,Elkamhawy, Ahmed,Paik, Sora,Bua, Silvia,Ha Lee, So,Abdelgawad, Mohamed A.,Roh, Eun Joo,Eldehna, Wagdy M.,Supuran, Claudiu T.
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p. 1457 - 1464
(2019/08/26)
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- Fluorine walk: The impact of fluorine in quinolone amides on their activity against African sleeping sickness
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Human African Trypanosomiasis, also known as African sleeping sickness, is caused by the parasitic protozoa of the genus Trypanosoma. If there is no pharmacological intervention, the parasites can cross the blood-brain barrier (BBB), inevitably leading to death of the patients. Previous investigation identified the quinolone amide GHQ168 as a promising lead compound having a nanomolar activity against T. b. brucei. Here, the role of a fluorine substitution at different positions was investigated in regard to toxicity, pharmacokinetics, and antitrypanosomal activity. This ‘fluorine walk’ led to new compounds with improved metabolic stability and consistent activity against T. b. brucei. The ability of the new quinolone amides to cross the BBB was confirmed using an 18F-labelled quinolone amide derivative by means of ex vivo autoradiography of a murine brain.
- Berninger, Michael,Erk, Christine,Fu?, Antje,Skaf, Joseph,Al-Momani, Ehab,Israel, Ina,Raschig, Martina,Güntzel, Paul,Samnick, Samuel,Holzgrabe, Ulrike
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supporting information
p. 377 - 391
(2018/05/22)
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- Quinolone amides as antitrypanosomal lead compounds with In Vivo activity
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Human African trypanosomiasis (HAT) is a major tropical disease for which few drugs for treatment are available, driving the need for novel active compounds. Recently, morpholino-substituted benzyl amides of the fluoroquinolone-type antibiotics were identified to be compounds highly active against Trypanosoma brucei brucei. Since the lead compound GHQ168 was challenged by poor water solubility in previous trials, the aim of this study was to introduce structural variations to GHQ168 as well as to formulate GHQ168 with the ultimate goal to increase its aqueous solubility while maintaining its in vitro antitrypanosomal activity. The pharmacokinetic parameters of spray-dried GHQ168 and the newly synthesized compounds GHQ242 and GHQ243 in mice were characterized by elimination half-lives ranging from 1.5 to 3.5 h after intraperitoneal administration (4 mice/compound), moderate to strong human serum albumin binding for GHQ168 (80%) and GHQ243 (45%), and very high human serum albumin binding (>99%) for GHQ242. For the lead compound, GHQ168, the apparent clearance was 112 ml/h and the apparent volume of distribution was 14 liters/kg of body weight (BW). Mice infected with T. b. rhodesiense (STIB900) were treated in a stringent study scheme (2 daily applications between days 3 and 6 postinfection). Exposure to spray-dried GHQ168 in contrast to the control treatment resulted in mean survival durations of 17 versus 9 days, respectively, a difference that was statistically significant. Results that were statistically insignificantly different were obtained between the control and the GHQ242 and GHQ243 treatments. Therefore, GHQ168 was further profiled in an early-treatment scheme (2 daily applications at days 1 to 4 postinfection), and the results were compared with those obtained with a control treatment. The result was statistically significant mean survival times exceeding 32 days (end of the observation period) versus 7 days for the GHQ168 and control treatments, respectively. Spray-dried GHQ168 demonstrated exciting antitrypanosomal efficacy.
- Hiltensperger, Georg,Hecht, Nina,Kaiser, Marcel,Rybak, Jens-Christoph,Hoerst, Alexander,Dannenbauer, Nicole,Müller-Buschbaum, Klaus,Bruhn, Heike,Esch, Harald,Lehmann, Leane,Meinel, Lorenz,Holzgrabe, Ulrike
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supporting information
p. 4442 - 4452
(2016/08/02)
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- MONOCARBOXYLATE TRANSPORT MODULATORS AND USES THEREOF
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The invention generally relates to the field of monocarboxylate transport modulators, e.g., monocarboxylate transport inhibitors, and more particularly to new substituted-quinolone compounds, the synthesis and use of these compounds and their pharmaceutical compositions, e.g., in treating, modulating, forestalling and/or reducing physiological conditions associated with monocarboxylate transport activity such as in treating cancer and other neoplastic disorders, inflammatory diseases, disorders of abnormal tissue growth and fibrosis including cardiomyopathy, obesity, diabetes, cardiovascular diseases, tissue and organ transplant rejection, and malaria.
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Paragraph 0091
(2016/06/20)
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- An operational transformation of 3-carboxy-4-quinolones into 3-nitro-4-quinolones via ipso-nitration using polysaccharide supported copper nanoparticles: Synthesis of 3-tetrazolyl bioisosteres of 3-carboxy-4-quinolones as antibacterial agents
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Chitosan supported Cu nano-particles have been synthesized, and utilized for the synthesis of 3-nitro-4-quinolones from 3-carboxy-4-quinolones via ipso nitration. The synthesized 3-nitro derivatives of 4-quinolones were successfully converted into their 3-tetrazolyl bioisosteres which showed increased antibacterial activity as compared to the standard ciprofloxacin.
- Azad, Chandra S.,Narula, Anudeep K.
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p. 19052 - 19059
(2016/03/01)
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- Rational design of partial agonists for the muscarinic M1 acetylcholine receptor
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Aiming to design partial agonists for a G-protein-coupled receptor based on dynamic ligand binding, we synthesized three different series of bipharmacophoric ligands composed of the orthosteric building blocks iperoxo and 1 linked to allosteric modulators (BQCA-derived compounds, BQCAd; TBPB-derived compound, TBPBd). Their interactions were studied with the human muscarinic acetylcholine M1-receptor (hM1) with respect to receptor binding and Gq-protein signaling. Results demonstrate that iperoxo/BQCAd (2, 3) and 1/BQCAd hybrids (4) act as M1 partial agonists, whereas 1/TBPBd hybrids (5) did not activate M1-receptors. Among the iperoxo/BQCAd-hybrids, spacer length in conjunction with the pattern of substitution tuned efficacy. Most interestingly, a model of dynamic ligand binding revealed that the spacer length of 2a and 3a controlled the probability of switch between the inactive purely allosteric and the active bitopic orthosteric/allosteric binding pose. In summary, dynamic ligand binding can be exploited in M1 receptors to design partial agonists with graded efficacy.
- Chen, Xinyu,Kl?ckner, Jessika,Holze, Janine,Zimmermann, Cornelia,Seemann, Wiebke K.,Schrage, Ramona,Bock, Andreas,Mohr, Klaus,Tr?nkle, Christian,Holzgrabe, Ulrike,Decker, Michael
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p. 560 - 576
(2015/01/30)
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- Operative conversions of 3-carboxy-4-quinolones into 3-nitro-4-quinolones via ipso-nitration: Potential antifilarial agents as inhibitors of Brugia malayi thymidylate kinase
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An efficient, cost effective and green methodology for ipso nitration in the synthesis of the 3-nitro derivative of 3-carboxy 4-quinolones has been developed by the quantitative use of copper acetate and silver nitrate in water. The observed regioselectivity of nitration is explained by the DFT calculations. Three of these compounds with IC50 values (2.9-3.4 μmol) against Brugia malayi thymidylate kinase may be good antifilarial agents as also evidenced by molecular docking studies.
- Azad, Chandra S.,Balaramnavar, Vishal M.,Khan, Imran A.,Doharey, Pawan K.,Saxena, Jitendra K.,Saxena, Anil K.
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p. 82208 - 82214
(2015/10/12)
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- Synthesis and biological evaluation of a class of quinolone triazoles as potential antimicrobial agents and their interactions with calf thymus DNA
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A novel series of quinolone triazoles were synthesized and characterized by IR, NMR, MS and HRMS spectra. All the newly prepared compounds were screened for their antimicrobial activities against seven bacteria and four fungi. Bioactive assay manifested that most of new compounds exhibited good or even stronger antibacterial and antifungal activities against the tested strains including multi-drug resistant MRSA in comparison with reference drugs Norfloxacin, Chloromycin and Fluconazole. The preliminary interactive investigations of compound 6b with calf thymus DNA by fluorescence and UV-vis spectroscopic methods revealed that compound 6b could effectively intercalate DNA to form compound 6b-DNA complex which might block DNA replication and thus exert its antimicrobial activities.
- Cui, Sheng-Feng,Ren, Yu,Zhang, Shao-Lin,Peng, Xin-Mei,Damu, Guri L.V.,Geng, Rong-Xia,Zhou, Cheng-He
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p. 3267 - 3272
(2013/06/27)
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- HAPTENS AND IMMUNOREACTIVE AGENTS AND USE THEREOF FOR PRODUCING FAMILY ANTIBODIES AND IMMUNOASSAYS FOR QUINOLONES
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The invention relates to haptens, immunogens and secondary immunoreactive agents, to the use thereof for producing wide-spectrum antibodies against quinolone-type antibiotics, to the application thereof to immunochemical analysis techniques, and to a kit enabling the detection of said antibiotics in biological samples from food products of animal origin.
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Paragraph 0057; 0058
(2013/10/21)
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- HAPTENS AND IMMUNOREACTIVE AGENTS AND USE THEREOF FOR PRODUCING FAMILY ANTIBODIES AND IMMUNOASSAYS FOR QUINOLONES
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The invention relates to haptens, immunogens and secondary immunoreactive agents, to the use thereof for producing wide-spectrum antibodies against quinolone-type antibiotics, to the application thereof to immunochemical analysis techniques, and to a kit enabling the detection of said antibiotics in biological samples from food products of animal origin.
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Paragraph 0081; 0097-0099
(2013/10/22)
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- Synthesis and study of 1-ethyl-3-carbohydrazide and 3-[1-oxo-2-hydrazino-3- {p-toluenesulfon}]quinolone derivatives against bacterial infections
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We have synthesized newer series of quinolone derivatives substituted with hydrazine group (6a-e) and sulfonamide group (7a-e). These compounds were screened for antibacterial activity. All these compounds were fully characterized by spectroscopic means and elemental analysis. From minimum inhibitory concentration (MIC) data, it has been observed that all the synthesized compounds exhibited good antibacterial activity in vitro.
- Srivastava, Nivedita,Kumar, Anil
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p. 464 - 468
(2013/10/01)
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- Identification and characterisation of small-molecule inhibitors of Rv3097c-encoded lipase (LipY) of Mycobacterium tuberculosis that selectively inhibit growth of bacilli in hypoxia
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The mycobacterial Rv3097c-encoded lipase LipY is considered as a true lipase involved in the hydrolysis of triacylglycerol stored in lipid inclusion bodies for the survival of dormant mycobacteria. To date, orlistat is the only known LipY inhibitor. In view of the important emerging role of this enzyme, a search for small-molecule inhibitors of LipY was made, leading to the identification of some new compounds (8a-8d, 8f, 8h and 8i) with potent inhibitory activities against recombinant LipY, with no cytotoxicity [50% inhibitory concentration (CC50) ≥500 μg/mL]. The compounds 6a, 8c and 8f potently inhibited (>90%) the growth of Mycobacterium tuberculosis H37Rv grown under hypoxia (oxygen-depleted condition) but had no effect on aerobically grown bacilli, suggesting that these new small molecules are highly selective towards the growth inhibition of hypoxic cultures of M. tuberculosis and hence provide new leads for combating latent tuberculosis.
- Saxena, Anil K.,Roy, Kuldeep K.,Singh, Supriya,Vishnoi,Kumar, Anil,Kashyap, Vivek Kr.,Kremer, Laurent,Srivastava, Ranjana,Srivastava, Brahm S.
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- Synthesis, characterization and pharmacological studies of some substituted fluoroquinolones
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Certain N-1 substituted fluoroquinolonic derivatives were synthesized and evaluated for antimicrobial and antioxidant activities. N-1 alkyl/ aryl/ aryl sulphonyl substituted derivatives of the title compounds have been synthesized to identify newer fluoroquinolones which have better efficacy, lesser side effects and well tolerability. The biological evaluation of the synthesized fluoroquinolone derivatives was carried out using agar-well diffusion method and compounds FI-ETH, FII-SUL, FIII-ATY, FIV-BZO, and FV-BZY were found to be active against both Gram-positive and Gram-negative bacteria having activity comparable to that of standard drug i.e. Ofloxacin 10mg/ml. N-1 substituted moiety is mostly active against strain is S. aureus, K. Pneumonia, and E. coli with concentration of 100 - 150μg/ml, and less active against strain is B. subtilis. And secondly, antioxidant activity is that of show the better activity by this four method DPPH Free Radical Scavenging Assay, Hydrogen Peroxide Radical Scavenging Activity, Nitric Oxide Assay, and Reducing Power Assay. All the synthesized compounds show the better antioxidant activity and in fourth one method result is mostly capable reducing power activity of the synthesized compounds.
- Abdullah, Faiz Mohd.,Singh, Arvind Kumar
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p. 609 - 615
(2013/11/06)
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- Synthesis and in vitro antiplasmodial activities of fluoroquinolone analogs
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Fluoroquinolone analogs were synthesized by simple alkylation followed by click chemistry and evaluated for their antimalarial in vitro against chloroquine sensitive strain of Plasmodium falciparum while ciprofloxacin was used as standard. Our results showed that the compound 12 was found most active with IC50 value of 1.33 μg/mL while ciprofloxacin showed IC 50 = 8.81 μg/mL. Therefore, screening of either known or unknown quinolone/fluoroquinolone analogs are worthwhile to find more potent antimalarial drugs which might prove useful in the treatment of mild or severe malaria in human either alone or in combination with existing antimalarial drugs.
- Dixit, Sandeep K.,Mishra, Nidhi,Sharma, Manish,Singh, Shailja,Agarwal, Alka,Awasthi, Satish K.,Bhasin
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experimental part
p. 52 - 59
(2012/07/28)
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- Synthesis and structure-activity relationships of new quinolone-type molecules against trypanosoma brucei
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Human African trypanosomiasis (HAT) or sleeping sickness is caused by two subspecies of Trypanosoma brucei, Trypanosoma brucei gambiense, and Trypanosoma brucei rhodesiense and is one of Africa's old plagues. It causes a huge number of infections and cases of death per year because, apart from limited access to health services, only inefficient chemotherapy is available. Since it was reported that quinolones such as ciprofloxacin show antitrypanosomal activity, a novel quinolone-type library was synthesized and tested. The biological evaluation illustrated that 4-quinolones with a benzylamide function in position 3 and cyclic or acyclic amines in position 7 exhibit high antitrypanosomal activity. Structure-activity relationships (SAR) are established to identify essential structural elements. This analysis led to lead structure 29, which exhibits promising in vitro activity against T. b. brucei (IC50 = 47 nM) and T. b. rhodesiense (IC50 = 9 nM) combined with low cytotoxicity against macrophages J774.1. Screening for morphological changes of trypanosomes treated with compounds 19 and 29 suggested differences in the morphology of mitochondria of treated cells compared to those of untreated cells. Segregation of the kinetoplast is hampered in trypanosomes treated with these compounds; however, topoisomerase II is probably not the main drug target.
- Hiltensperger, Georg,Jones, Nicola G.,Niedermeier, Sabine,Stich, August,Kaiser, Marcel,Jung, Jamin,Puhl, Sebastian,Damme, Alexander,Braunschweig, Holger,Meinel, Lorenz,Engstler, Markus,Holzgrabe, Ulrike
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scheme or table
p. 2538 - 2548
(2012/05/19)
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- Synthesis of novel α-amino acid functionalized 6-fluoro quinolones, their antibacterial activity and molecular docking studies
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A series of novel α-amino acid functionalized 6-fluoro quinolone derivatives have been synthesized from quinoline ester 2 in series of steps with good yields. The compounds have been screened against gram-positive and gram-negative bacteria in-vitro. Some compounds show promising activity against all species of gram-positive and gram-negative bacteria, with reference to standard Norfloxacin as well as Ciprofloxacin. The activity data is validated by molecular docking studies and are in good co-relation with observed trends.
- Venkat Lingaiah,Yakaiah,Chandra Shekhar,Ravi Kumar,Sathaiah,Raju,Shanthan Rao,Narsaiah,Pranay Kumar,Murthy,Purushotham,Narahari Sastry
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scheme or table
p. 969 - 980
(2012/10/08)
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- A small-molecule inhibitor of nipah virus envelope protein-mediated membrane fusion
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Nipah virus (NiV), a highly pathogenic paramyxovirus, causes respiratory disease in pigs and severe febrile encephalitis in humans with high mortality rates. On the basis of the structural similarity of viral fusion (F) proteins within the family Paramyxoviridae, we designed and tested 18 quinolone derivatives in a NiV and measles virus (MV) envelope protein-based fusion assay beside evaluation of cytotoxicity. We found five compounds successfully inhibiting NiV envelope protein-induced cell fusion. The most active molecules (19 and 20), which also inhibit the syncytium formation induced by infectious NiV and show a low cytotoxicity in Vero cells, represent a promising lead quinolone-type compound structure. Molecular modeling indicated that compound 19 fits well into a particular protein cavity present on the NiV F protein that is important for the fusion process. 2009 American Chemical Society.
- Niedermeier, Sabine,Singethan, Katrin,Rohrer, Sebastian G.,Matz, Magnus,Kossner, Markus,Diederich, Sandra,Maisner, Andrea,Schmitz, Jens,Hiltensperger, Georg,Baumann, Knut,Holzgrabe, Ulrike,Schneider-Schaulies, Jurgen
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supporting information; experimental part
p. 4257 - 4265
(2010/03/04)
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- Microwave-assisted simple synthesis of substituted 4-quinolone derivatives
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A simple and efficient method was developed for the synthesis of 4-quinolone-3-carboxylic esters and 4-quinolone-3-carbonitriles under microwave (MW) activation using anilines and acrylates as materials. All reactions demonstrated the benefits of microwave reactions: convenient operation, short reaction time, and good yields.
- Cao, Xin,You, Qi-Dong,Li, Zhi-Yu,Yang, Yan,Wang, Xiao-Jian
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experimental part
p. 4375 - 4383
(2010/05/01)
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- Novel fluoroquinolones: Design, synthesis, and in vivo activity in mice against Mycobacterium tuberculosis H37Rv
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Novel 6,8-difluoro-1-alkyl-5-amino-1,4-dihydro-4-oxo-7-{4-substituted piperazin-1-yl}-quinoline-3-carboxylic acids, with the substituents at 4th position of piperazine being -[2(pyridine-4-carbonyl) hydrazono]propyl and -2 [(pyrazine-2-carbonyl) amino] ethyl, were synthesized and evaluated in vivo against Mycobacterium tuberculosis H37Rv in Swiss albino mice. Test compounds exhibited activity comparable to that of sparfloxacin (survival rate, reduction of splenomegaly and reduced tubercular lesions) at a dose of 200 mg/kg.
- Shindikar, Anand V.,Viswanathan
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p. 1803 - 1806
(2007/10/03)
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- Synthesis of 6-fluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid derivatives as potential antimicrobial agents
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In the present study, a series of 1-ethyl/benzyl-6-fluoro-7-(substituted piperazin-1-yl)1,4-dihydro-4-oxo-quinoline-3-carboxylic acid were synthesized and characterized by IR, 1H-NMR, mass spectral and elemental analysis. The in vitro antibacterial and antifungal activities of the compounds were evaluated by paper disc diffusion method. The minimum inhibitory concentrations (MIC) of the compounds were also determined by agar streak dilution method. The in vivo antibacterial activity of the compounds against Escherichia coli was also evaluated by mouse protection test. All the compounds exhibited significant antibacterial and weak antifungal activities. The in vivo antibacterial activity (ED50) against E. coli was 50-160 mg kg -1 in the order of 7100 μg mL-1 against Staphylococcus aureus, Staphylococcus epidermidis, Micrococcus luteus, Bacillus cereus, E. coli, Klebsiella pneumoniae, Candida albicans and Aspergillus niger.
- Rameshkumar, Natesh,Ashokkumar, Mohan,Subramanian, Ekambaram Harihara,Ilavarasan, Raju,Sridhar, Seshaiah Krishnan
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p. 1001 - 1004
(2007/10/03)
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- Microwave assisted Gould-Jacob reaction: Synthesis of 4-quinolones under solvent free conditions
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A single step Gould-Jacob reaction between aromatic amines and diethyl ethoxymethylenemalonates (EMME) for the synthesis of 4-quinolones under solvent free microwave irradiation has been carried out and compared with classical heating.
- Dave, Chaitanya G.,Joshipura, Hardik M.
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p. 650 - 652
(2007/10/03)
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- A clay catalyzed method for diethyl 2,2,2- trichloroethylidenepropanedioate, an efficient intermediate for the synthesis of enamino esters
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An improved high yielding procedure for diethyl 2,2,2- trichloroethyledinepropanedioate (3) using montmorillonite K-10 catalyst has been described. Various diethyl (substituted aminomethylene)propanedioates (6a-j) have been synthesised in excellent yields starting from propanedioate (3) via addition products (5a-j).
- Deshmukh,Panse,Bhawal
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p. 1801 - 1809
(2007/10/03)
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- An NMR study of halogenated 1,4-dihydro-1-ethyl-4-oxoquinoline-3-carboxylates
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Ethyl 1,4-dihydro-1-ethyl-4-oxoquinoline-3-carboxylate and 29 of its mono-, di-and tri-fluoro and/or -chloro derivatives were synthesized and their 1H, 13C and 19F NMR spectra were recorded. 1H, 13C and 19F chemical shifts, JHH, JFH, JCF and JFF coupling constants are reported. The 13C substituent chemical shift values of the chloro and fluoro substituents were calculated by linear multiple regression.
- Podanyi, Benjamin,Kereszturi, Geza,Vasvari-Debreczy, Lelle,Chinoin, Istvan Hermecz,Toth, Gabor
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p. 972 - 978
(2007/10/03)
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- Tautomerism and acidity in 4-quinolone-3-carboxylic acid derivatives
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Prototropic tautomerism in 4-quinolone-3-carboxylic acid derivatives has been studied with particular emphasis on the influence of the ring substituents on the equilibrium. The techniques used include UV, 1H-NMR, 13C-NMR (solution and 13C-NMR CP/MAS (solid state) and semiempirical and ab initio calculations. The pKa values of some quinolone derivatives have been determined and correlated with data obtained from semiempirical methods.
- De La Cruz, Angeles,Elguero, Jose,Goya, Pilar,Martinez, Ana,Pfleiderer, Wolfgang
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p. 6135 - 6150
(2007/10/02)
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- Structure-Activity Relationships of Antibacterial 6,7- and 7,8-Disubstituted 1-Alkyl-1,4-dihydro-4-oxoquinoline-3-carboxylic Acids
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Previous quantitative and qualitative structure-activity studies in antibacterial monosubstituted 1-ethyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acids prompted us to synthesize the 6,7,8-polysubstituted compounds.In this paper, the preparation and antibacterial activity of the 6,7- and 7,8-disubstituted compounds and their derivatives are described.Among these compounds, 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)quinoline-3-carboxylic acid (34) possessed many significant activities and was more active than oxolinic acid (84) against Gram-positive andGram-negative bacteria.Structure activity relationships are discussed.
- Koga, Hiroshi,Itoh, Akira,Murayama, Satoshi,Suzue, Seigo,Irikura, Tsutomu
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p. 1358 - 1363
(2007/10/02)
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