scholarly journals Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

2016 ◽  
Vol 12 ◽  
pp. 769-795 ◽  
Author(s):  
Daniel Wiegmann ◽  
Stefan Koppermann ◽  
Marius Wirth ◽  
Giuliana Niro ◽  
Kristin Leyerer ◽  
...  
Keyword(s):  
Natural Products ◽  
Antibacterial Agents ◽  
Peptide Antibiotics ◽  
Peptidoglycan Biosynthesis ◽  
Sar Studies ◽  
Current State ◽  
Naturally Occurring ◽  
Structure Activity ◽  
Key Enzyme ◽  
State Of Research

Muraymycins are a promising class of antimicrobial natural products. These uridine-derived nucleoside-peptide antibiotics inhibit the bacterial membrane protein translocase I (MraY), a key enzyme in the intracellular part of peptidoglycan biosynthesis. This review describes the structures of naturally occurring muraymycins, their mode of action, synthetic access to muraymycins and their analogues, some structure–activity relationship (SAR) studies and first insights into muraymycin biosynthesis. It therefore provides an overview on the current state of research, as well as an outlook on possible future developments in this field.

scholarly journals Unexpected Seven-Membered Ring Formation for Muraymycin-Type Nucleoside-Peptide Antibiotics

Molbank ◽  
10.3390/m1122 ◽  
2020 ◽  
Vol 2020 (2) ◽  
pp. M1122 ◽  
Author(s):  
Kristin Leyerer ◽  
Stefan Koppermann ◽  
Christian Ducho
Keyword(s):  
Building Block ◽  
Antibacterial Agents ◽  
Solid Support ◽  
Membered Ring ◽  
Peptide Antibiotics ◽  
Sar Studies ◽  
Naturally Occurring ◽  
Structure Activity ◽  
Major Interest ◽  
Subsequent Cyclization

Naturally occurring nucleoside-peptide antibiotics such as muraymycins or caprazamycins are of major interest for the development of novel antibacterial agents. However, the synthesis of new analogues of these natural products for structure–activity relationship (SAR) studies is challenging. In our synthetic efforts towards a muraymycin-derived nucleoside building block suitable for attachment to a solid support, we came across an interesting side product. This compound resulted from an undesired Fmoc deprotection with subsequent cyclization, thus furnishing a remarkable caprazamycin-like seven-membered diazepanone ring.

Glutathione S-transferase- and acetylcholinesterase-inhibiting natural products from medicinally important plants

2007 ◽  
Vol 79 (12) ◽  
pp. 2269-2276 ◽  
Author(s):  
Athar Ata ◽  
Stephanie A. Van Den Bosch ◽  
Drew J. Harwanik ◽  
Grant E. Pidwinski
Keyword(s):  
Natural Products ◽  
Enzyme Inhibitors ◽  
Glutathione S Transferase ◽  
Ache Inhibitors ◽  
Sar Studies ◽  
Naturally Occurring ◽  
Structure Activity ◽  
Potential Applications ◽  
Drug Discovery Program ◽  
Antiparasitic Agents

Naturally occurring enzyme inhibitors play an important role in a drug discovery program. Glutathione S-transferases (GSTs) play a significant role in the detoxification and metabolism of many xenobiotic and endobiotic compounds. GSTs are considered to be responsible for decreasing the effectiveness of anticancer/antiparasitic agents used for the treatment of cancer and parasitic diseases. The effectiveness of these biomedical agents may be improved by using GST inhibitors as an adjuvant during chemotherapy. Acetylcholinesterase (AChE) inhibitors have potential applications in curing cardiac problems and Alzheimer's disease. This article describes the identification of natural products exhibiting GST and AChE inhibitory activities, from medicinally important plants. Results obtained from the structure-activity relationship (SAR) studies of some of these newly discovered enzyme inhibitors are also discussed.

scholarly journals Aminoribosylated Analogues of Muraymycin Nucleoside Antibiotics

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3085 ◽  
Author(s):  
Daniel Wiegmann ◽  
Stefan Koppermann ◽  
Christian Ducho
Keyword(s):  
Structural Motif ◽  
The Novel ◽  
Reference Compound ◽  
Inhibitory Potency ◽  
Nucleoside Antibiotics ◽  
Peptidoglycan Biosynthesis ◽  
Sar Studies ◽  
Naturally Occurring ◽  
Key Enzyme

Nucleoside antibiotics are uridine-derived natural products that inhibit the bacterial membrane protein MraY. MraY is a key enzyme in the membrane-associated intracellular stages of peptidoglycan biosynthesis and therefore considered to be a promising, yet unexploited target for novel antibacterial agents. Muraymycins are one subclass of such naturally occurring MraY inhibitors. As part of structure-activity relationship (SAR) studies on muraymycins and their analogues, we now report on novel derivatives with different attachment of one characteristic structural motif, i.e., the aminoribose moiety normally linked to the muraymycin glycyluridine core unit. Based on considerations derived from an X-ray co-crystal structure, we designed and synthesised muraymycin analogues having the aminoribose attached (via a linker) to either the glycyluridine amino group or to the uracil nucleobase. Reference compounds bearing the non-aminoribosylated linker units were also prepared. It was found that the novel aminoribosylated analogues were inactive as MraY inhibitors in vitro, but that the glycyluridine-modified reference compound retained most of the inhibitory potency relative to the unmodified parent muraymycin analogue. These results point to 6′-N-alkylated muraymycin analogues as a potential novel variation of the muraymycin scaffold for future SAR optimisation.

scholarly journals Synthesis and Antibacterial Evaluation of N-phenylacetamide Derivatives Containing 4-Arylthiazole Moieties

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1772
Author(s):  
Hui Lu ◽  
Xia Zhou ◽  
Lei Wang ◽  
Linhong Jin
Keyword(s):  
Antibacterial Agents ◽  
Antibacterial Activities ◽  
Effective Concentration ◽  
Nematicidal Activity ◽  
Xanthomonas Oryzae ◽  
Membrane Rupture ◽  
Sar Studies ◽  
Structure Activity ◽  
Antibacterial Evaluation

A series of new N-phenylacetamide derivatives containing 4-arylthiazole moieties was designed and synthesized by introducing the thiazole moiety into the amide scaffold. The structures of the target compounds were confirmed by 1H-NMR, 13C-NMR and HRMS. Their in vitro antibacterial activities were evaluated against three kinds of bacteria—Xanthomonas oryzae pv. Oryzae (Xoo), Xanthomonas axonopodis pv. Citri (Xac) and X.oryzae pv. oryzicola (Xoc)—showing promising results. The minimum 50% effective concentration (EC50) value of N-(4-((4-(4-fluoro-phenyl)thiazol-2-yl)amino)phenyl)acetamide (A1) is 156.7 µM, which is superior to bismerthiazol (230.5 µM) and thiodiazole copper (545.2 µM). A scanning electron microscopy (SEM) investigation has confirmed that compound A1 could cause cell membrane rupture of Xoo. In addition, the nematicidal activity of the compounds against Meloidogyne incognita (M. incognita) was also tested, and compound A23 displayed excellent nematicidal activity, with mortality of 100% and 53.2% at 500 μg/mL and 100 μg/mL after 24 h of treatment, respectively. The preliminary structure-activity relationship (SAR) studies of these compounds are also briefly described. These results demonstrated that phenylacetamide derivatives may be considered as potential leads in the design of antibacterial agents.

Naturally occurring enzyme inhibitors and their pharmaceutical applications

2011 ◽  
Vol 83 (9) ◽  
pp. 1741-1749 ◽  
Author(s):  
Athar Ata ◽  
Samina Naz ◽  
Evan M. Elias
Keyword(s):  
Enzyme Inhibitors ◽  
Senile Dementia ◽  
Discovery Process ◽  
Drug Discovery Process ◽  
Ache Inhibitors ◽  
Sar Studies ◽  
Naturally Occurring ◽  
Structure Activity ◽  
Antiparasitic Drug

Enzyme inhibitors play a significant role in the drug discovery process. For instance, acetylcholinesterase (AChE) inhibitors have applications in curing Alzheimer’s disease (AD), senile dementia, ataxia, myasthenia gravis, and Parkinson’s disease. Glutathione S-transferase (GST) inhibitors have applications as adjuvants to overcome anticancer and antiparasitic drug resistance problems. Compounds inhibiting the activity of α-glucosidase are used to treat type 2 diabetes mellitus and obesity problems. This article describes the identification of natural products exhibiting AChE, GST, and α-glucosidase inhibitory activities from medicinally important plants. Additionally, structure–activity relationship (SAR) studies of these newly discovered enzyme inhibitors are also discussed.

scholarly journals Structure-Activity Relationship (SAR) Studies on Oxazolidinone Antibacterial Agents. 1. Conversion of 5-Substituent on Oxazolidinone.

2001 ◽  
Vol 49 (4) ◽  
pp. 347-352 ◽  
Author(s):  
Ryukou TOKUYAMA ◽  
Yoshiei TAKAHASHI ◽  
Yayoi TOMITA ◽  
Tomio SUZUKI ◽  
Toshihiko YOSHIDA ◽  
...  
Keyword(s):  
Antibacterial Agents ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Sar Studies ◽  
Structure Activity

scholarly journals Chemo- and site-selective derivatizations of natural products enabling biological studies

2014 ◽  
Vol 31 (3) ◽  
pp. 318-334 ◽  
Author(s):  
Omar Robles ◽  
Daniel Romo
Keyword(s):  
Natural Products ◽  
Functional Group ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Reactive Group ◽  
Bioactive Natural Products ◽  
Sar Studies ◽  
Structure Activity ◽  
Biological Studies ◽  
Site Selective

The direct chemo- and site-selective modification of native bioactive natural products (NP) for structure–activity relationship (SAR) studies and cellular probe synthesis has recently begun to be addressed (FG = functional group). This review highlights selected recent examples of these functionalization strategies, including those that simultaneously introduce a linker and reactive group (gray structure) for subsequent conjugation to reporter tags.

ChemInform Abstract: Muraymycin Nucleoside-Peptide Antibiotics: Uridine-Derived Natural Products as Lead Structures for the Development of Novel Antibacterial Agents

ChemInform ◽  
2016 ◽  
Vol 47 (22) ◽  
Author(s):  
Daniel Wiegmann ◽  
Stefan Koppermann ◽  
Marius Wirth ◽  
Giuliana Niro ◽  
Kristin Leyerer ◽  
...  
Keyword(s):  
Natural Products ◽  
Antibacterial Agents ◽  
Peptide Antibiotics
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