- Microwave-enhanced Friedl?nder synthesis for the rapid assembly of halogenated quinolines with antibacterial and biofilm eradication activities against drug resistant and tolerant bacteria
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Herein, we disclose the development of a catalyst- and protecting-group-free microwave-enhanced Friedl?nder synthesis which permits the single-step, convergent assembly of diverse 8-hydroxyquinolines with greatly improved reaction yields over traditional oil bath heating (increased from 34% to 72%). This rapid synthesis permitted the discovery of novel biofilm-eradicating halogenated quinolines (MBECs = 1.0-23.5 μM) active against MRSA, MRSE, and VRE. These small molecules exhibit activity through mechanisms independent of membrane lysis, further demonstrating their potential as a clinically useful treatment option against persistent biofilm-associated infections.
- Garrison, Aaron T.,Abouelhassan, Yasmeen,Yang, Hongfen,Yousaf, Hussain H.,Nguyen, Tho J.,Huigens, Robert W.III.
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supporting information
p. 720 - 724
(2017/04/27)
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- COMBINATION THERAPY FOR TREATING INFECTIONS DISEASES
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The present invention provides compositions comprising a quinoline, a potentiating agent, and optionally a pharmaceutically acceptable carrier, for treating and/or preventing infectious diseases. The provided compositions may also include another therapeutic agent (e.g., antibiotic). The provided compositions may be useful in treating and/or preventing bacterial infections as well as inhibiting and eradicating biofilm formation.
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Paragraph 00245
(2016/10/11)
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- A Phytochemical-Halogenated Quinoline Combination Therapy Strategy for the Treatment of Pathogenic Bacteria
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With the continued rise of drug-resistant bacterial infections coupled with the current discouraging state of the antibiotic pipeline, the need for new antibacterial agents that operate through unique mechanisms compared with conventional antibiotics and work in synergy with other agents is at an all-time high. We have discovered that gallic acid, a plant-derived phytochemical, dramatically potentiates the antibacterial activities of several halogenated quinolines (up to 11 800-fold potentiation against Staphylococcus aureus) against pathogenic bacteria, including drug-resistant clinical isolates. S. aureus demonstrated the highest sensitivity towards gallic acid-halogenated quinoline combinations, including one halogenated quinoline that demonstrated potentiation of biofilm eradication activity against a methicillin-resistant S. aureus (MRSA) clinical isolate. During our studies, we also demonstrated that these halogenated quionlines operate through an interesting metal(II) cation-dependent mechanism and display promising mammalian cytotoxicity.
- Abouelhassan, Yasmeen,Garrison, Aaron T.,Bai, Fang,Norwood, Verrill M.,Nguyen, Minh Thu,Jin, Shouguang,Huigens, Robert W.
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supporting information
p. 1157 - 1162
(2015/07/07)
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- New calcium-selective smart contrast agents for magnetic resonance imaging
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Calcium plays a vital role in the human body and especially in the central nervous system. Precise maintenance of Ca2+ levels is very crucial for normal cell physiology and health. The deregulation of calcium homeostasis can lead to neuronal cell death and brain damage. To study this functional role played by Ca2+ in the brain noninvasively by using magnetic resonance imaging, we have synthesized a new set of Ca2+-sensitive smart contrast agents (CAs). The agents were found to be highly selective to Ca 2+ in the presence of other competitive anions and cations in buffer and in physiological fluids. The structure of CAs comprises Gd3+-DO3A (DO3A=1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane) coupled to a Ca2+ chelator o-amino phenol-N,N,O-triacetate (APTRA). The agents are designed to sense Ca2+ present in extracellular fluid of the brain where its concentration is relatively high, that is, 1.2-0.8 mM. The determined dissociation constant of the CAs to Ca2+ falls in the range required to sense and report changes in extracellular Ca2+ levels followed by an increase in neural activity. In buffer, with the addition of Ca2+ the increase in relaxivity ranged from 100-157 %, the highest ever known for any T1-based Ca2+-sensitive smart CA. The CAs were analyzed extensively by the measurement of luminescence lifetime measurement on Tb 3+ analogues, nuclear magnetic relaxation dispersion (NMRD), and 17O NMR transverse relaxation and shift experiments. The results obtained confirmed that the large relaxivity enhancement observed upon Ca 2+ addition is due to the increase of the hydration state of the complexes together with the slowing down of the molecular rotation and the retention of a significant contribution of the water molecules of the second sphere of hydration. Smart Ca2+ sensing in the brain: To study Ca2+ in the brain noninvasively by magnetic resonance imaging, a new set of Ca2+-sensitive smart contrast agents (CAs) have been synthesized. The agents were found to be highly selective to Ca2+ in the presence of other competitive anions and cations in buffer and in physiological fluids. The determined dissociation constant of the CAs to Ca 2+ falls in the range required to sense and report changes in extracellular Ca2+ levels in response to neural activity (see figure). Copyright
- Verma, Kirti Dhingra,Forgacs, Attila,Uh, Hyounsoo,Beyerlein, Michael,Maier, Martin E.,Petoud, Stephane,Botta, Mauro,Logothetis, Nikos K.
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p. 18011 - 18026
(2014/01/17)
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- A facile synthesis of 2-methylquinolines via Pd-catalyzed aza-Wacker oxidative cyclization
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(Chemical Equation Presented) A novel Pd-catalyzed Wacker-type oxidative cyclization under air is described. By using this cyclization, a series of 2-methylquinolines are readily prepared with good yields under mild conditions.
- Zhang, Zuhui,Tan, Jiajing,Wang, Zhiyong
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p. 173 - 175
(2008/09/18)
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- REMEDIAL AGENT FOR CHRONIC ARTICULAR RHEUMATISM
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The present invention relates to an excellent remedial agent for chronic rheumatoid arthritis, comprising an aminostilbazole, derivative represented by the following formula [1] or a salt thereof as an active ingredient:A-B-D-E Wherein A represents hetero
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- MEDICINES
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The present inevntion relates to an excellent Vpr function regulating agent, comprising an aminostilbazole derivative represented by the following formula [1] or a salt thereof as an active ingredient:A-B-D-E wherein A represents heteroaryl or an oxide th
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Page/Page column 7
(2010/02/05)
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- Clay supported ammonium nitrate "clayan": A new reagent for selective nitration of arenes
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The nitration of activated, deactivated and highly functionalized arenes is described using clay-supported ammonium nitrate in the presence of perchloric acid.
- Meshram,Ganesh,Madhavi,Eshwaraiah,Yadav,Gunasekar
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p. 2497 - 2503
(2007/10/03)
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- Synthesis and biological activity and some aporphine derivatives related to apomorphine
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Several aporphine derivatives related to apomorphine were synthesized and evaluated for antihypertensive and central dopaminergic activity. Apocodeine and (6aR) 10,11 methylenedioxyaporphine produced apomorphine like postural asymmetries in caudate lesioned mice but were less potent than apomorphine in this respect. Of the aporphine derivatives tested for antihypertensive activity, 11 hydroxyaporphine proved to be the most potent upon oral administration to spontaneously hypertensive rats.
- Saari,King,Lotti,Scriabine
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p. 1086 - 1090
(2007/10/04)
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