- Synthesis, antimicrobial evaluation, and in silico studies of quinoline—1H-1,2,3-triazole molecular hybrids
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Abstract: Antimicrobial resistance has become a significant threat to global public health, thus precipitating an exigent need for new drugs with improved therapeutic efficacy. In this regard, molecular hybridization is deemed as a viable strategy to afford multi-target-based drug candidates. Herein, we report a library of quinoline—1H-1,2,3-triazole molecular hybrids synthesized via copper(I)-catalyzed azide-alkyne [3 + 2] dipolar cycloaddition reaction (CuAAC). Antimicrobial evaluation identified compound 16 as the most active hybrid in the library with a broad-spectrum antibacterial activity at an MIC80 value of 75.39?μM against methicillin-resistant S. aureus, E. coli, A. baumannii, and multidrug-resistant K. pneumoniae. The compound also showed interesting antifungal profile against C. albicans and C. neoformans at an MIC80 value of 37.69 and 2.36?μM, respectively, superior to fluconazole. In vitro toxicity profiling revealed non-hemolytic activity against human red blood cells (hRBC) but partial cytotoxicity to human embryonic kidney cells (HEK293). Additionally, in silico studies predicted excellent drug-like properties and the importance of triazole ring in stabilizing the complexation with target proteins. Overall, these results present compound 16 as a promising scaffold on which other molecules can be modeled to deliver new antimicrobial agents with improved potency. Graphic abstract: [Figure not available: see fulltext.].
- Awolade, Paul,Cele, Nosipho,Kerru, Nagaraju,Singh, Parvesh
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p. 2201 - 2218
(2020/06/17)
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- Redox responsive Pd(ii) templated rotaxane nanovalve capped mesoporous silica nanoparticles: A folic acid mediated biocompatible cancer-targeted drug delivery system
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In this study, we report a redox responsive drug delivering nanocarrier design based on mesoporous silica nanoparticles. Gatekeeping of the mesopore is achieved using Pd(ii) templated, mechanically interlocked rotaxane nanovalves with a folic acid terminal group, anchored by a disulfide bridge as a snap-top on the surface. The active metal templated rotaxane approach helps in quick and irreversible gate formation for effective utilization of the drug. The folic acid head group bestows targeting capability, specifically to cancer cells. Once nanoparticles enter the cancer cell, controlled release of the cargo is triggered by cleavage of the disulfide bond using an endogenous glutathione stimulus. In addition to having efficient drug loading and controlled release mechanisms, this smart biocompatible carrier system showed obvious uptake and consequent release of the drug in HeLa cells, demonstrating its use as a potential theranostic material. This journal is
- Gayam, Srivardhan Reddy,Wu, Shu-Pao
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supporting information
p. 7009 - 7016
(2015/02/19)
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- A novel diketopyrrolopyrrole (DPP)-based [2]rotaxane for highly selective optical sensing of fluoride
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A novel [2]rotaxane based on an orthogonal H-bonded motif and 3,6-di(thiophen-2-yl)pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione (DPP) with controlled topicity was successfully constructed, displaying excellent stimulated responses toward anion and solvent polarity. The preorganized host selectively recognized F- with high optical sensitivity and reversibility via enhanced positive cooperativity and noncovalent interaction by evidence of a shorter fluorescence lifetime.
- Raju, Mandapati V. Ramakrishnam,Lin, Hong-Cheu
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supporting information
p. 1274 - 1277
(2013/05/09)
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- Amide derivatives
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The invention concerns novel phenoxyacetic acid amide derivatives of the formula I (and pharmaceutically acceptable salts thereof) in which R1 is hydrogen or fluoro, R2 is phenyl, cycloalkyl, alkyl or alkenyl as defined herein, and R3 is hydrogen, methyl or ethyl, or R2 and R3 together form polymethylene as defined herein. The invention also includes pharmaceutical compositions containing the amide derivatives, means for the manufacture of the said derivatives and for their use in the treatment of obesity and related conditions and/or in the manufacture of novel medicaments.
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- Phenyl ethers
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The invention concerns a series of novel phenoxyacetic acid ethers (and pharmaceutically acceptable salts thereof) of the formula I in which R1 is H or F, R2 and R3 are H or (1-3C)alkyl, Z is CH2 OH or a group -
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