An Extended Phosphate Linkage: Synthesis, Hybridization and Modeling Studies of Modified Oligonucleotides

1996 ◽  
Vol 15 (7-8) ◽  
pp. 1383-1395 ◽  
Author(s):  
Becky Haly ◽  
Laurent Bellon † ◽  
Venkatraman Mohan ◽  
Yogesh Sanghvi
Keyword(s):  
Modified Oligonucleotides ◽  
Modeling Studies ◽  
Phosphate Linkage ◽  
Linkage Synthesis

Synthesis and hybridization property of sugar and phosphate linkage modified oligonucleotides

1999 ◽  
Vol 7 (7) ◽  
pp. 1467-1473 ◽  
Author(s):  
Lak Shin Jeong ◽  
Ji Hea Lee ◽  
Kyeong-Eun Jung ◽  
Hyung Ryong Moon ◽  
Kichul Kim ◽  
...  
Keyword(s):  
Modified Oligonucleotides ◽  
Phosphate Linkage

Synopsis of Epidemic Modeling Studies

2001 ◽  
Author(s):  
Jr Bombardt ◽  
John N.
Keyword(s):  
Epidemic Modeling ◽  
Modeling Studies

p-Trifluoroacetophenone Oxime Ester Derivatives: Synthesis, Antimicrobial and Cytotoxic Evaluation and Molecular Modeling Studies

2020 ◽  
Vol 17 (2) ◽  
pp. 169-183 ◽  
Author(s):  
İrem Bozbey ◽  
Suat Sari ◽  
Emine Şalva ◽  
Didem Kart ◽  
Arzu Karakurt
Keyword(s):  
Molecular Modeling ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cells ◽  
Cytotoxic Agents ◽  
Human Neuroblastoma Cell ◽  
Human Neuroblastoma ◽  
Modeling Studies ◽  
Broth Microdilution Method ◽  
Molecular Modeling Studies

Background: Azole antifungals are among the first-line drugs clinically used for the treatment of systemic candidiasis, a deadly type of fungal infection that threatens mostly immunecompromised and hospitalized patients. Some azole derivatives were also reported to have antiproliferative effects on cancer cells. Objective: In this study, 1-(4-trifluoromethylphenyl)-2-(1H-imidazol-1-yl)ethanone (3), its oxime (4), and a series of its novel oxime ester derivatives (5a-v) were synthesized and tested for their in vitro antimicrobial activities against certain ATCC standard strains of Candida sp. fungi and bacteria. The compounds were also tested for their cytotoxic effects against mouse fibroblast and human neuroblastoma cell lines. Molecular modeling studies were performed to provide insights into their possible mechanisms for antifungal and antibacterial actions. Methods: The compounds were synthesized by the reaction of various oximes with acyl chlorides. Antimicrobial activity of the compounds was determined according to the broth microdilution method. For the determination of cytotoxic effect, we used MTS assay. Molecular docking and QM/MM studies were performed to predict the binding mechanisms of the active compounds in the catalytic site of C. albicans CYP51 (CACYP51) and S. aureus flavohemoglobin (SAFH), the latter of which was created via homology modeling. Results: 5d, 5l, and 5t showed moderate antifungal activity against C. albicans, while 3, 5c, and 5r showed significant antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. Most of the compounds showed approximately 40-50% inhibition against the human neuroblastoma cells at 100 µM. In this line, 3 was the most potent with an IC50 value of 82.18 μM followed by 5a, 5o, and 5t. 3 and 5a were highly selective to the neuroblastoma cells. Molecular modelling results supported the hypothesis that our compounds were inhibitors of CAYP51 and SAFH. Conclusion: This study supports that oxime ester derivatives may be used for the development of new antimicrobial and cytotoxic agents.

Computational Approaches as Rational Decision Support Systems for Discovering Next-Generation Antitubercular Agents: Mini-Review

2019 ◽  
Vol 15 (5) ◽  
pp. 369-383
Author(s):  
Rahul Balasaheb Aher ◽  
Kunal Roy
Keyword(s):  
Recent Progress ◽  
Neglected Tropical Diseases ◽  
Acyl Carrier Protein ◽  
Thioredoxin Reductase ◽  
Protein Tyrosine Phosphatases ◽  
Antitubercular Agents ◽  
Computer Aided Drug Design ◽  
Modeling Studies ◽  
Catalase Peroxidase ◽  
Molecular Modeling Studies

Tuberculosis, malaria, dengue, chikungunya, leishmaniasis etc. are a large group of neglected tropical diseases that prevail in tropical and subtropical countries, affecting one billion people every year. Minimal funding and grants for research on these scientific problems challenge many researchers to find a different way to reduce the extensive time and cost involved in the drug discovery cycle of these problems. Computer-aided drug design techniques have already been proved successful in the discovery of new molecules rationally by reducing the time and cost involved in the development of drugs. In the current minireview, we are highlighting on the molecular modeling studies published during 2010-2018 for target specific antitubercular agents. This review includes the studies of Structure-Based (SB) and Ligand-Based (LB) modeling and those involving Machine Learning (ML) techniques against different antitubercular targets such as dihydrofolate reductase (DHFR), enoyl Acyl Carrier Protein (ACP) reductase (InhA), catalase-peroxidase (KatG), enzyme antigen 85C, protein tyrosine phosphatases (PtpA and PtpB), dUTPase, thioredoxin reductase (MtTrxR), etc. The information presented in this review will help the researchers to get acquainted with the recent progress in the modeling studies of antitubercular agents.

Click conjugation of 4'-C-modified oligonucleotides

2011 ◽  
Author(s):  
Anu Kiviniemi ◽  
Pasi Virta ◽  
Harri Lönnberg
Keyword(s):  
Modified Oligonucleotides

scholarly journals Triazole-Modified Nucleic Acids for the Application in Bioorganic and Medicinal Chemistry

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 628
Author(s):  
Dagmara Baraniak ◽  
Jerzy Boryski
Keyword(s):  
Nucleic Acids ◽  
State Of The Art ◽  
Modified Oligonucleotides ◽  
Synthetic Genes ◽  
Chemically Modified ◽  
Amide Linkage ◽  
Dna And Rna ◽  
Modified Dna ◽  
Modified Nucleic Acids ◽  
Non Coding Rnas

This review covers studies which exploit triazole-modified nucleic acids in the range of chemistry and biology to medicine. The 1,2,3-triazole unit, which is obtained via click chemistry approach, shows valuable and unique properties. For example, it does not occur in nature, constitutes an additional pharmacophore with attractive properties being resistant to hydrolysis and other reactions at physiological pH, exhibits biological activity (i.e., antibacterial, antitumor, and antiviral), and can be considered as a rigid mimetic of amide linkage. Herein, it is presented a whole area of useful artificial compounds, from the clickable monomers and dimers to modified oligonucleotides, in the field of nucleic acids sciences. Such modifications of internucleotide linkages are designed to increase the hybridization binding affinity toward native DNA or RNA, to enhance resistance to nucleases, and to improve ability to penetrate cell membranes. The insertion of an artificial backbone is used for understanding effects of chemically modified oligonucleotides, and their potential usefulness in therapeutic applications. We describe the state-of-the-art knowledge on their implications for synthetic genes and other large modified DNA and RNA constructs including non-coding RNAs.

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