- Alkyl-Aryl-Vancomycins: Multimodal Glycopeptides with Weak Dependence on the Bacterial Metabolic State
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Resistance to last-resort antibiotics such as vancomycin for Gram-positive bacterial infections necessitates the development of new therapeutics. Furthermore, the ability of bacteria to survive antibiotic therapy through formation of biofilms and persiste
- Sarkar, Paramita,Basak, Debajyoti,Mukherjee, Riya,Bandow, Julia E.,Haldar, Jayanta
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Read Online
- An example of green surfactant systems based on inherently biodegradable IL-derived amphiphilic oximes
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Progress in the development of biodegradable ionic liquids (ILs) leads to designing green surfactant formulations for miscellaneous applications. In this work, we present synthesis of a series of novel IL-derived amphiphilic pyridinium oximes composed by
- Gathergood, Nicholas,Ghosh, Kallol K.,Kapitanov, Illia V.,Karpichev, Yevgen,Pandya, Subhashree Jayesh,Sahu, Reshma,Sinha, Deepak,Usmani, Zeba
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- Low-toxicity amphiphilic molecules linked by an aromatic nucleus show broad-spectrum antibacterial activity and low drug resistance
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Amphiphilic molecules linked by an aromatic nucleus were developed that showed high selectivity toward bacteria over mammalian cells, and low drug resistance. A promising compound 4g exhibited strong bactericidal activity against a panel of sensitive and resistant bacteria, low toxicity, the ability to reduce cell viability in biofilms, stability in mammalian fluids, rapid killing of pathogens, and high in vivo efficacy against methicillin-resistant Staphylococcus aureus (MRSA).
- Chu, Wenchao,Yang, Yi,Qin, Shangshang,Cai, Jianfeng,Bai, Mengmeng,Kong, Hongtao,Zhang, En
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supporting information
p. 4307 - 4310
(2019/04/17)
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- Small antibacterial molecules highly active against drug-resistant: Staphylococcus aureus
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The rapid growth of antibiotic resistance in Staphylococcus aureus coupled with their biofilm forming ability has made the infections difficult to treat with conventional antibiotics. This has created a massive threat towards public health and is a huge concern worldwide. Aiming to address this challenging issue, herein we report a new class of small antibacterial molecules (SAMs) with high antibacterial activity against multidrug-resistant S. aureus. The design principle of the molecules was based on the variation of hydrophobic/hydrophilic balance through incorporation of two quaternary ammonium groups, ethanol moieties, non-peptidic amide bonds and aliphatic chains. The lead compound, identified through a comprehensive analysis of structure-activity relationships, displayed high activity against clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) with MIC values in the range of 1-4 μg mL-1. More importantly, this compound was capable of killing stationary phase bacteria and disrupting established biofilms of MRSA. Additionally, the compound revealed minimum toxicity towards human erythrocytes (HC50 = 577 μg mL-1) and did not show significant toxicity towards mammalian cells (MDCK and A549) up to 128 μg mL-1. Remarkably, the incorporation of non-peptidic amide bonds made the compounds less susceptible to degradation in human plasma, serum and mouse liver homogenate. Taken together, the results therefore indicate great promise for this class of molecules to be developed as potent antibacterial agents in treating infections caused by drug-resistant S. aureus.
- Dey, Rajib,De, Kathakali,Mukherjee, Riya,Ghosh, Sreyan,Haldar, Jayanta
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supporting information
p. 1907 - 1915
(2019/11/20)
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- Amide aromatic phenol antibacterial peptide analogue with antibacterial activity and preparation method thereof
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The invention belongs to the technical field of pharmaceutical chemistry, and discloses an amide aromatic phenol antibacterial peptide analogue with drug-resistance bacteria resistant activity and without obvious toxicity and a preparation method thereof. The target product is obtained by 3-4 reaction steps, and the main structure of the product is shown as follows. In-vitro antibacterial activityexperiments prove that most of the series of compounds have excellent activity on Gram-positive staphylococcus aureus and enterococcus faecalis, Gram-negative Escherichia coli and stenotrophomonas maltophilia, and the compounds have excellent broad spectrum antibacterial activity; moreover, in-vitro red cell hemolytic data is low in toxicity and has excellent selectivity. One part of the compounds also have excellent antibacterial activity on 'superbacteria' comprising drug-resistant methicillin staphylococcus aureus (MRSA), clinical strains producing enzymes NDM-1 and KPC-2 and the like. Therefore, the series of compounds are expected to serve as novel antibacterial candidate drugs.
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Paragraph 0085; 0086; 0094
(2018/12/03)
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- Antibacterial and Antibiofilm Activity of Cationic Small Molecules with Spatial Positioning of Hydrophobicity: An in Vitro and in Vivo Evaluation
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More than 80% of the bacterial infections are associated with biofilm formation. To combat infections, amphiphilic small molecules have been developed as promising antibiofilm agents. However, cytotoxicity of such molecules still remains a major problem. Herein we demonstrate a concept in which antibacterial versus cytotoxic activities of cationic small molecules are tuned by spatial positioning of hydrophobic moieties while keeping positive charges constant. Compared to the molecules with more pendent hydrophobicity from positive centers (MIC = 1-4 μg/mL and HC50 = 60-65 μg/mL), molecules with more confined hydrophobicity between two centers show similar antibacterial activity but significantly less toxicity toward human erythrocytes (MIC = 1-4 μg/mL and HC50 = 805-1242 μg/mL). Notably, the optimized molecule is shown to be nontoxic toward human cells (HEK 293) at a concentration at which it eradicates established bacterial biofilms. The molecule is also shown to eradicate preformed bacterial biofilm in vivo in a murine model of superficial skin infection.
- Hoque, Jiaul,Konai, Mohini M.,Sequeira, Shanola S.,Samaddar, Sandip,Haldar, Jayanta
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p. 10750 - 10762
(2016/12/16)
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- Membrane Active Small Molecules Show Selective Broad Spectrum Antibacterial Activity with No Detectable Resistance and Eradicate Biofilms
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Treating bacterial biofilms with conventional antibiotics is limited due to ineffectiveness of the drugs and higher propensity to develop bacterial resistance. Development of new classes of antibacterial therapeutics with alternative mechanisms of action has become imperative. Herein, we report the design, synthesis, and biological evaluations of novel membrane-active small molecules featuring two positive charges, four nonpeptidic amide groups, and variable hydrophobic/hydrophilic (amphiphilic) character. The biocides synthesized via a facile methodology not only displayed good antibacterial activity against wild-type bacteria but also showed high activity against various drug-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE), and β-lactam-resistant Klebsiella pneumoniae. Further, these biocides not only inhibited the formation of biofilms but also disrupted the established S. aureus and E. coli biofilms. The membrane-active biocides hindered the propensity to develop bacterial resistance. Moreover, the biocides showed negligible toxicity against mammalian cells and thus bear potential to be used as therapeutic agents.
- Hoque, Jiaul,Konai, Mohini M.,Gonuguntla, Spandhana,Manjunath, Goutham B.,Samaddar, Sandip,Yarlagadda, Venkateswarlu,Haldar, Jayanta
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p. 5486 - 5500
(2015/08/03)
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- Enhanced activity of fluorinated quaternary ammonium surfactants against Pseudomonas aeruginosa
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A novel series of fluorinated quaternary bisammonium surfactants has been synthesized in view to optimize their antimicrobial activities against Pseudomonas aeruginosa. As compared with commercial references, most of the new surfactants synthesized exhibit an enhanced activity which is discussed as a function of the nature of the spacer group between the quaternized nitrogen atoms and of the nature of the connector function between the nitrogen atoms and the perfluorinated carbon chains. It appears that the fluorinated "Gemini" surfactants bearing an amide connector can be an interesting alternative to hydrocarbon ammonium salts as preservatives and disinfectants against P. aeruginosa.
- Massi, Lionel,Guittard, Frederic,Levy, Richard,Geribaldi
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experimental part
p. 1615 - 1622
(2009/06/20)
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- Preparation and antimicrobial behaviour of gemini fluorosurfactants
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The introduction of perfluorinated chains in the molecular structure of quaternary ammonium gemini surfactants have led to particularly active antimicrobial agents evaluated in this work. Connectors and spacers were studied in relation with antimicrobial
- Massi, Lionel,Guittard, Frederic,Levy, Richard,Duccini, Yves,Geribaldi, Serge
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p. 519 - 523
(2007/10/03)
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- One-pot conversion of t-butyl carbamates to amides with acyl halide-methanol mixtures
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Acyl halide-methanol mixtures are efficient reagents for the one-pot transformation of t-butyl carbamates into amides. This transformation can be carried out in the presence of a benzyloxycarbonyl group.
- Nazih, Abdesslame,Heissler, Denis
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p. 203 - 206
(2007/10/03)
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