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.

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 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 Synthetic Chiral Derivatives of Xanthones: Biological Activities and Enantioselectivity Studies

Molecules ◽  
2019 ◽  
Vol 24 (4) ◽  
pp. 791 ◽  
Author(s):  
Carla Fernandes ◽  
Maria Carraro ◽  
João Ribeiro ◽  
Joana Araújo ◽  
Maria Tiritan ◽  
...  
Keyword(s):  
Biological Activity ◽  
Biological Activities ◽  
Pharmacological Activities ◽  
Sar Studies ◽  
Naturally Occurring ◽  
Structure Activity ◽  
Wide Range ◽  
Synthetic Methodologies ◽  
Derivatives Of ◽  
Biological And Pharmacological Activities

Many naturally occurring xanthones are chiral and present a wide range of biological and pharmacological activities. Some of them have been exhaustively studied and subsequently, obtained by synthesis. In order to obtain libraries of compounds for structure activity relationship (SAR) studies as well as to improve the biological activity, new bioactive analogues and derivatives inspired in natural prototypes were synthetized. Bioactive natural xanthones compromise a large structural multiplicity of compounds, including a diversity of chiral derivatives. Thus, recently an exponential interest in synthetic chiral derivatives of xanthones (CDXs) has been witnessed. The synthetic methodologies can afford structures that otherwise could not be reached within the natural products for biological activity and SAR studies. Another reason that justifies this trend is that both enantiomers can be obtained by using appropriate synthetic pathways, allowing the possibility to perform enantioselectivity studies. In this work, a literature review of synthetic CDXs is presented. The structures, the approaches used for their synthesis and the biological activities are described, emphasizing the enantioselectivity studies.

scholarly journals Structure-Activity Relationship (SAR) Studies on Oxazolidinone Antibacterial Agents. 3. Synthesis and Evaluation of 5-Thiocarbamate Oxazolidinones.

2001 ◽  
Vol 49 (4) ◽  
pp. 361-367 ◽  
Author(s):  
Ryukou TOKUYAMA ◽  
Yoshiei TAKAHASHI ◽  
Yayoi TOMITA ◽  
Masatoshi TSUBOUCHI ◽  
Nobuhiko IWASAKI ◽  
...  
Keyword(s):  
Antibacterial Agents ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Sar Studies ◽  
Structure Activity

scholarly journals Polymer-Supported Synthesis of Various Pteridinones and Pyrimidodiazepinones

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1603
Author(s):  
Jan Chasák ◽  
Lucie Brulíková
Keyword(s):  
Building Block ◽  
Solid Phase ◽  
Structure Activity Relationship ◽  
Synthetic Methods ◽  
Activity Relationship ◽  
Synthetic Approach ◽  
Sar Studies ◽  
Structure Activity ◽  
Pharmacokinetic Properties ◽  
Polymer Supported

In this report, we employed the solid-phase synthetic approach to prepare variously substituted dihydropteridinones, tetrahydropyrrolopteridinones, and pyrimidodiazepinones, using a versatile building block-4,6-dichloro-5-nitropyrimidine. All these compounds are pharmacologically significant scaffolds of the great importance of medicinal chemists. The fast and efficient synthetic methodology is highly desirable for defining their structure-activity relationship (SAR) and optimizing pharmacokinetic properties. Our research efforts utilize simple synthetic methods to generate a library of analogues for future SAR studies. The efficiency of our approach was exemplified in various pteridinones as well as pyrimidodiazepinones.

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.

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