Prodrugs of Analogs of Nucleic Acid Components

1994 ◽  
Vol 59 (10) ◽  
pp. 2127-2165 ◽  
Author(s):  
Petr Alexander ◽  
Antonín Holý
Keyword(s):  
Nucleic Acid ◽  
Anticancer Activity ◽  
Rational Design ◽  
Therapeutic Agents ◽  
Nucleotide Analogues ◽  
Structural Association

This review regards various attitudes to the rational design of prodrugs derived of nucleoside and nucleotide analogues with pronounced biological (antiviral, anticancer) activity. Particular attention is focused on the recent development of prodrugs of approved therapeutic agents with the above structural association.

Molecular insights on the dynamic stability of peptide nucleic acid functionalized carbon and boron nitride nanotubes

2021 ◽  
Vol 23 (1) ◽  
pp. 219-228
Author(s):  
Nabanita Saikia ◽  
Mohamed Taha ◽  
Ravindra Pandey
Keyword(s):  
Nucleic Acid ◽  
Boron Nitride ◽  
Nucleic Acids ◽  
Dynamic Stability ◽  
Peptide Nucleic Acid ◽  
Rational Design ◽  
Peptide Nucleic Acids ◽  
Boron Nitride Nanotubes ◽  
Molecular Hybrids ◽  
Single Wall Nanotubes

The rational design of self-assembled nanobio-molecular hybrids of peptide nucleic acids with single-wall nanotubes rely on understanding how biomolecules recognize and mediate intermolecular interactions with the nanomaterial's surface.

Novel 1,2,3-Triazole-functionalized pyrido[3',2':4,5]furo[3,2-d]pyrimidin- 4(3H)-one Derivatives: Synthesis, Anticancer Activity, CoMFA and CoMSIA Studies

2020 ◽  
Vol 17 (12) ◽  
pp. 969-978
Author(s):  
Balakishan Vadla ◽  
Sailu Betala
Keyword(s):  
Anticancer Activity ◽  
Cell Line ◽  
Normal Cell ◽  
Rational Design ◽  
Human Cancer ◽  
Strong Basis ◽  
Hek 293 ◽  
Normal Cell Line ◽  
Human Cancer Cell Lines ◽  
Mcf 7

A series of novel triazole functionalized pyrido [3',2':4,5] furo[3,2-d] pyrimidin-4 (3H)-one derivatives 7a-p were prepared from ethyl furo[2,3-b]pyridine-2-carboxylate 3 on reaction with ammonia to afford furo[2,3-b]pyridine-2-carboxamide 4. This compound, on reaction with triethyl orthoformate TEOF, gave compound 5. Compound 5 on propargylation, followed by a reaction with substituted aryl azides under Sharpless reaction conditions, furnished triazole tagged pyrido [3',2':4,5]furo[3,2-d] pyrimidin-4(3H)-one derivatives. All the products 7a-p were screened against four human cancer cell lines, such as HeLa - Cervical cancer (CCL-2), COLO 205- Colon cancer (CCL-222), HepG2- Liver cancer (HB-8065), and MCF7 - Breast cancer (HTB-22) and one normal cell line (HEK 293). Compounds 7b, 7n, 7o and 7p, which showed promising anticancer activity, were identified and found to be non-toxic to normal cell line. Studies for HeLa, COLO205, HepG2, and MCF-7 using CoMFA and CoMSIA were carried out . Models from 3D-QSAR provided a strong basis for future rational design of more active and selective HeLa, COLO205, HepG2, and MCF-7 cell line inhibitors.

scholarly journals Bile Acid Conjugates with Anticancer Activity: Most Recent Research

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 25
Author(s):  
Maria Luisa Navacchia ◽  
Elena Marchesi ◽  
Daniela Perrone
Keyword(s):  
Bile Acid ◽  
Cancer Therapy ◽  
Anticancer Activity ◽  
Bile Acids ◽  
Treatment Modality ◽  
Biological Properties ◽  
Therapeutic Agents ◽  
Bioactive Molecules ◽  
Hybrid Functional ◽  
Hybrid Molecules

The advantages of a treatment modality that combines two or more therapeutic agents in cancer therapy encourages the study of hybrid functional compounds for pharmacological applications. In light of this, we reviewed recent works on hybrid molecules based on bile acids. Due to their biological properties, as well as their different chemical/biochemical reactive moieties, bile acids can be considered very interesting starting molecules for conjugation with natural or synthetic bioactive molecules.

scholarly journals Locked nucleic acid as a novel class of therapeutic agents

RNA Biology ◽  
2009 ◽  
Vol 6 (3) ◽  
pp. 321-323 ◽  
Author(s):  
Rakesh N. Veedu ◽  
Jesper Wengel
Keyword(s):  
Nucleic Acid ◽  
Therapeutic Agents ◽  
Locked Nucleic Acid

scholarly journals A journey in bioinspired supramolecular chemistry: from molecular tweezers to small molecules that target myotonic dystrophy

2016 ◽  
Vol 12 ◽  
pp. 125-138 ◽  
Author(s):  
Steven C Zimmerman
Keyword(s):  
Small Molecules ◽  
Supramolecular Chemistry ◽  
Myotonic Dystrophy ◽  
Small Molecule ◽  
Early Life ◽  
Rational Design ◽  
Early Experience ◽  
Therapeutic Agents ◽  
Early Career ◽  
Molecular Tweezers

This review summarizes part of the author’s research in the area of supramolecular chemistry, beginning with his early life influences and early career efforts in molecular recognition, especially molecular tweezers. Although designed to complex DNA, these hosts proved more applicable to the field of host–guest chemistry. This early experience and interest in intercalation ultimately led to the current efforts to develop small molecule therapeutic agents for myotonic dystrophy using a rational design approach that heavily relies on principles of supramolecular chemistry. How this work was influenced by that of others in the field and the evolution of each area of research is highlighted with selected examples.

scholarly journals Developing Picornaviruses for Cancer Therapy

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 685 ◽  
Author(s):  
Cormac McCarthy ◽  
Nadishka Jayawardena ◽  
Laura N. Burga ◽  
Mihnea Bostina
Keyword(s):  
Cancer Therapy ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Rna Viruses ◽  
Therapeutic Agents ◽  
Oncolytic Viruses ◽  
Wide Range ◽  
Positive Sense

Oncolytic viruses (OVs) form a group of novel anticancer therapeutic agents which selectively infect and lyse cancer cells. Members of several viral families, including Picornaviridae, have been shown to have anticancer activity. Picornaviruses are small icosahedral non-enveloped, positive-sense, single-stranded RNA viruses infecting a wide range of hosts. They possess several advantages for development for cancer therapy: Their genomes do not integrate into host chromosomes, do not encode oncogenes, and are easily manipulated as cDNA. This review focuses on the picornaviruses investigated for anticancer potential and the mechanisms that underpin this specificity.

scholarly journals Strategies to Enhance Drug Absorption via Nasal and Pulmonary Routes

Pharmaceutics ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 113 ◽  
Author(s):  
Maliheh Ghadiri ◽  
Paul Young ◽  
Daniela Traini
Keyword(s):  
Nucleic Acid ◽  
Tight Junction ◽  
Drug Absorption ◽  
Therapeutic Agents ◽  
Nasal Administration ◽  
Absorption Enhancers ◽  
Non Invasive ◽  
Basic Concepts ◽  
Transmucosal Administration ◽  
Poor Absorption

New therapeutic agents such as proteins, peptides, and nucleic acid-based agents are being developed every year, making it vital to find a non-invasive route such as nasal or pulmonary for their administration. However, a major concern for some of these newly developed therapeutic agents is their poor absorption. Therefore, absorption enhancers have been investigated to address this major administration problem. This paper describes the basic concepts of transmucosal administration of drugs, and in particular the use of the pulmonary or nasal routes for administration of drugs with poor absorption. Strategies for the exploitation of absorption enhancers for the improvement of pulmonary or nasal administration are discussed, including use of surfactants, cyclodextrins, protease inhibitors, and tight junction modulators, as well as application of carriers such as liposomes and nanoparticles.

scholarly journals Higher Order Architecture of Designer Peptides Forms Bioinspired 10 nm siRNA Delivery System

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Alicia Gamboa ◽  
Selina F. Urfano ◽  
Katrina Hernandez ◽  
Deborah A. Fraser ◽  
Luladey Ayalew ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Delivery System ◽  
Rational Design ◽  
Sirna Delivery ◽  
Higher Order ◽  
Collagen Peptide ◽  
Complex Forms ◽  
Quaternary Structures ◽  
Quaternary Complex ◽  
Sirna Delivery System

AbstractThe higher-order architecture observed in biological systems, like viruses, is very effective in nucleic acid transport. The replications of this system has been attempted with both synthetic and naturally occurring polymers with mixed results. Here we describe a peptide/siRNA quaternary complex that functions as an siRNA delivery system. The rational design of a peptide assembly is inspired by the viral capsids, but not derived from them. We selected the collagen peptide (COL) to provide the structural stability and the folding framework, and hybridize it with the cell penetrating peptide (CPP) that allows for effective penetration of biological barriers. The peptide/siRNA quaternary complex forms stoichiometric, 10 nm nanoparticles, that show fast cellular uptake (<30 min), effective siRNA release, and gene silencing. The complex provides capsid-like protection for siRNA against nucleases without being immunostimulatory, or cytotoxic. Our data suggests that delivery vehicles based on synthetic quaternary structures that exhibit higher-order architecture may be effective in improving delivery and release of nucleic acid cargo.

scholarly journals Use of Organosilicon Compounds towards the Rational Design of Antiparasitic and Antiviral Drugs

1995 ◽  
Vol 2 (3) ◽  
pp. 143-151 ◽  
Author(s):  
Gérard Déléris
Keyword(s):  
Reverse Transcriptase ◽  
Antisense Oligonucleotides ◽  
Rational Design ◽  
Chemical Properties ◽  
Therapeutic Agents ◽  
Main Group ◽  
Biologically Active ◽  
Hiv Reverse Transcriptase ◽  
Antiparasitic Drugs ◽  
High Level

One of the major problems met for the conception of antiviral or antiparasitic drugs is to reach a high level of selectivity towards the pathogenic agent versus the host. We shall describe two synthetic approaches where main group organometallics have been used towards this goal. A series of nucleoside sila-analogues was synthesized as potential therapeutic agents designed to inhibit HIV Reverse Transcriptase. In a second approach novel organosilicon derivatives have been synthesized as mimics of antisense oligonucleotides.Infectious agents, namely viruses or parasites, more or less use cellular machinery. Therefore therapeutic agents must interfere with biochemical mechanisms or possess high affinity towards specific molecular cellular components, to reach selectivity.We thought that main group organometallics could show many advantages for designing biologically active molecules in this field. They allow a high synthetic flexibility for the modulations of physico-chemical properties and they show a mechanistic behaviour which may be close to the one of several heteroelements present in living organisms such as sulfur or phosphorus.We tried to use this approach towards two directions involving the synthesis of organosilicon derivatives i.e:-the synthesis of organosilicon derivatives as inhibitors of HIV Reverse Transcriptase,-the synthesis of organosilicon precursors of modified antisense oligonucleotides.

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