2483-46-7Relevant articles and documents
Two-component dendritic gel: Effect of stereochemistry on the supramolecular chiral assembly
Hirst, Andrew R.,Smith, David K.,Feiters, Martin C.,Geurts, Huub P. M.
, p. 5901 - 5910 (2004)
The self-assembly of diaminododecane solubilised by four different stereoisomeric dendritic peptides to form gel-phase materials in toluene was investigated. The second generation dendritic peptides were based on D- and L-lysine building blocks, and each contained three chiral centres. By designing dendritic peptides in which the configurations of the chiral centres were modified, and applying them as gelator units, the assembly of stereoisomers could be investigated. In all cases, the self-assembly of gelator units resulted in macroscopic gelation. However, the degree of structuring was modulated by the stereoisomers employed, an effect which changed the morphology and macroscopic behavior of the self-assembled state. Enantiomeric (L,L,L or D,D,D) gelator units formed fibrous molecular assemblies, whilst the racemic gel (50% L,L,L: 50% D,D,D) formed a flat structure with a "woven" appearance. Gelator units based on L,D,D or D,L,L dendritic peptides also formed fibrous assemblies, but small-angle X-ray scattering indicated significant morphological differences were caused by the switch in chirality. Furthermore, the macroscopic stability of the gel was diminished when these peptides were compared with their L,L,L or D,D,D analogues. In this paper it is clearly shown that individual stereocentres, on the molecular level, are directly related to the helicity within the fibre. It is argued that the chirality controls the pattern of hydrogen bonding within the assembly, and hence determines the extent of fibre formation and the macroscopic gel strength.
Synthesis and antibacterial bioactivities of cationic deacetyl linezolid amphiphiles
Bai, Peng-Yan,Qin, Shang-Shang,Chu, Wen-Chao,Yang, Yi,Cui, De-Yun,Hua, Yong-Gang,Yang, Qian-Qian,Zhang, En
, p. 925 - 945 (2018)
Bacterial infections cause various life-threatening diseases and have become a serious public health problem due to the emergence of drug-resistant strains. Thus, novel antibiotics with excellent antibacterial activity and low cytotoxicity are urgently needed. Here, three series of novel cationic deacetyl linezolid amphiphiles bearing one lipophilic alkyl chain and one non-peptidic amide bond were synthesized and tested for antimicrobial activities. Several compounds showed excellent antibacterial activity toward drug-sensitive bacteria such as gram-negative bacteria Escherichia coli (E. coli), Salmonella enterica (S. enterica) and gram-positive Staphylococcus aureus (S. aureus), Enterococcus faecalis (E. faecalis). Moreover, these amphiphilic molecules also exhibited strong activity against drug-resistant species such as methicillin-resistant S. aureus (MRSA), KPC (Klebsiella pneumoniae carbapenemase) and NDM-1 (New Delhi metallo-β-lactamase 1) producing carbapenem-resistant Enterobacteriaceae (CRE). For example, the MICs (minimum inhibitory concentrations) of the best compound 6e, ranged from 2 to 16 μg/mL and linezolid ranged from 2 to >64 μg/mL against these strains. Therefore, 6e is a broad-spectrum antimicrobial compound that may be a suitable lead as an antibiotic. The molecule 6e were found to function primarily by permeabilization and depolarization of bacterial membranes. Importantly, bacterial resistance against compound 6e was difficult to induce, and 6e was stable under plasma conditions and showed suitable activity in mammalian plasma. Thus, these compounds can be further developed into a potential new class of broad-spectrum antibiotics.
Photocleavable antimicrobial peptide mimics for precluding antibiotic resistance
Feng, Yang,Zhang, Yang-Yang,Li, Ke,Tian, Na,Wang, Wei-Bo,Zhou, Qian-Xiong,Wang, Xue-Song
, p. 3192 - 3195 (2018)
Cationic amphiphiles featuring a lysine-based hydrophilic moiety, an alkyl chain-based hydrophobic moiety, and an o-nitrobenzyl group-based linker were constructed facilely, which show alkyl chain-dependent antibacterial activity against both Gram-positive and Gram-negative bacteria, low cytotoxicity toward mammalian cells, and UV-cleavable properties, representing a novel type of environmental accumulation-free antimicrobial peptide mimic.
Synthesis and evaluation of a bis-3-chloropiperidine derivative incorporating an anthraquinone pharmacophore
Zuravka, Ivonne,Sosic, Alice,Gatto, Barbara,G?ttlich, Richard
, p. 4606 - 4609 (2015)
With the aim to attain an alkylating agent with enhanced DNA-affinity, we have successfully synthesised lysine-linked bis-3-chloropiperidine 1 bearing an anthraquinone moiety known to bind double-stranded DNA. Consistent with our expectations, compound 1 appears to intercalate into the DNA double helix, which can be observed by conformational changes of plasmid DNA suggesting alkylation and intercalation-induced DNA unwinding. The results of this work can provide a meaningful starting point for investigating the molecular mechanism of action of this novel DNA alkylating conjugate 1 with improved affinity for DNA.
Appended Aromatic Moieties in Flexible Bis-3-chloropiperidines Confer Tropism against Pancreatic Cancer Cells
Carraro, Caterina,Helbing, Tim,Francke, Alexander,Zuravka, Ivonne,Sosic, Alice,De Franco, Michele,Gandin, Valentina,Gatto, Barbara,G?ttlich, D. Richard
, p. 860 - 868 (2020/12/07)
Nitrogen mustards (NMs) are an old but still largely diffused class of anticancer drugs. However, spreading mechanisms of resistance undermine their efficacy and therapeutic applicability. To expand their antitumour value, we developed bis-3-chloropiperidines (B-CePs), a new class of mustard-based alkylating agent, and we recently reported the striking selectivity for BxPC-3 pancreatic tumour cells of B-CePs bearing aromatic moieties embedded in the linker. In this study, we demonstrate that such tropism is shared by bis-3-chloropiperidines bearing appended aromatic groups in flexible linkers, whereas esters substituted by aliphatic groups or by efficient DNA-interacting groups are potent but nonselective cytotoxic agents. Besides, we describe how the critical balance between water stability and DNA reactivity can affect the properties of bis-3-chloropiperidines. Together, these findings support the exploitation of B-CePs as potential antitumour clinical candidates.
Rhamnolipid inspired lipopeptides effective in preventing adhesion and biofilm formation of Candida albicans
Jovanovic, Milos,Radivojevic, Jelena,O'Connor, Kevin,Blagojevic, Stevan,Begovic, Biljana,Lukic, Vera,Nikodinovic-Runic, Jasmina,Savic, Vladimir
supporting information, p. 209 - 217 (2019/03/23)
Rhamnolipids are biodegradable low toxic biosurfactants which exert antimicrobial and anti-biofilm properties. They have attracted much attention recently due to potential applications in areas of bioremediation, therapeutics, cosmetics and agriculture, however, the full potential of these versatile molecules is yet to be explored. Based on the facts that many naturally occurring lipopeptides are potent antimicrobials, our study aimed to explore the potential of replacing rhamnose in rhamnolipids with amino acids thus creating lipopeptides that would mimic or enhance properties of the parent molecule. This would allow not only for more economical and greener production but also, due to the availability of structurally different amino acids, facile manipulation of physico-chemical and biological properties. Our synthetic efforts produced a library of 43 lipopeptides revealing biologically more potent molecules. The structural changes significantly increased, in particular, anti-biofilm properties against Candida albicans, although surface activity of the parent molecule was almost completely abolished. Our findings show that the most active compounds are leucine derivatives of 3-hydroxy acids containing benzylic ester functionality. The SAR study demonstrated a further increase in activity with aliphatic chain elongation. The most promising lipopeptides 15, 23 and 36 at 12.5 μg/mL concentration allowed only 14.3%, 5.1% and 11.2% of biofilm formation, respectively after 24 h. These compounds inhibit biofilm formation by preventing adhesion of C. albicans to abiotic and biotic surfaces.
AMPHIPHILIC CONJUGATES OF TOBRAMYCIN LINKED TO A LYSINE-BASED PEPTOID MIMIC VIA A TETHER
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Page/Page column 24, (2018/11/22)
Amphiphilic conjugates of tobramycin linked to a lysine-based peptoid mimic via a tether are disclosed. Said lysine-based peptoid mimics comprise a positively-charged L-lysine, a hydrophobic aromatic core and an alkylene tether assembled through a tertiary amide linkage. Optimization of the resulting conjugate is provided using a C12 alkylene tether. These conjugates have utility as antibacterial agents, in particular when used in conjunction with another antibacterial agent (such as rifampicin or minocycline), where the combination results in a synergistic activity against drug-resistant bacteria (in particular extensively drug-resistant P. aeruginosa). As a result, these conjugates provide for effective antibiotic adjuvants that help overcome resistance of Gram-negative bacteria to antibiotics.