Triazolopyrimidine Nuclei: Privileged Scaffolds for Developing Antiviral Agents with a Proper Pharmacokinetic Profile

2021 ◽  
Vol 28 ◽  
Author(s):  
Tommaso Felicetti ◽  
Maria Chiara Pismataro ◽  
Violetta Cecchetti ◽  
Oriana Tabarrini ◽  
Serena Massari
Keyword(s):  
Viral Infections ◽  
Biological Activities ◽  
Antiviral Agents ◽  
Pharmacokinetic Profile ◽  
Binding Mode ◽  
Biologically Active ◽  
Dna Viruses ◽  
Pharmacokinetic Properties ◽  
Biological Target ◽  
Synthetic Methodologies

Viruses are a continuing threat to global health. The lack or limited therapeutic armamentarium against some viral infections and increasing drug resistance issues make the search for new antiviral agents urgent. In recent years, a growing literature highlighted the use of triazolopyrimidine (TZP) heterocycles in the development of antiviral agents, with numerous compounds that showed potent antiviral activities against different RNA and DNA viruses. TZP core represents a privileged scaffold for achieving biologically active molecules, thanks to: i) the synthetic feasibility that allows to variously functionalize TZPs in the different positions of the nucleus, ii) the ability of TZP core to establish multiple interactions with the molecular target, and iii) its favorable pharmacokinetic properties. In the present review, after mentioning selected examples of TZP-based compounds with varied biological activities, we will focus on those antivirals that appeared in the literature in the last 10 years. Approaches used for their identification, the hit-to-lead studies, and the emerged structure-activity relationship will be described. A mention of the synthetic methodologies to prepare TZP nuclei will also be given. In addition, their mechanism of action, the binding mode within the biological target, and pharmacokinetic properties will be analyzed, highlighting the strengths and weaknesses of compounds based on the TZP scaffold, which is increasingly used in medicinal chemistry.

Hybrids of Coumarin Derivatives as Potent and Multifunctional Bioactive Agents: A Review

2020 ◽  
Vol 16 (3) ◽  
pp. 272-306
Author(s):  
Ioannis Fotopoulos ◽  
Dimitra Hadjipavlou-Litina
Keyword(s):  
Pharmacological Activity ◽  
Biological Activities ◽  
Structural Characteristics ◽  
Pharmacokinetic Profile ◽  
Biologically Active ◽  
Hybridization Technique ◽  
Coumarin Derivatives ◽  
Hybrid Molecules ◽  
Pharmacokinetic Properties ◽  
Bioactive Agents

Background: Coumarins exhibit a plethora of biological activities, e.g. antiinflammatory and anti-tumor. Molecular hybridization technique has been implemented in the design of novel coumarin hybrids with several bioactive groups in order to obtain molecules with better pharmacological activity and improved pharmacokinetic profile. Objective: Therefore, we tried to gather as many as possible biologically active coumarin hybrids referred in the literature till now, to delineate the structural characteristics in relation to the activities and to have a survey that might help the medicinal chemists to design new coumarin hybrids with drug-likeness and varied bioactivities. Results: The biological activities of the hybrids in most of the cases were found to be different from the biological activities presented by the parent coumarins. The results showed that the hybrid molecules are more potent compared to the standard drugs used in the evaluation experiments. Conclusion: Conjugation of coumarin with varied pharmacophore groups/druglike molecules responsible for different biological activities led to many novel hybrid molecules, with a multitarget behavior and improved pharmacokinetic properties.

scholarly journals A REVIEW ON THE SYNTHETIC METHODOLOGIES OF CHROMONES

2018 ◽  
Vol 11 (12) ◽  
pp. 9 ◽  
Author(s):  
Mahathy Vanguru ◽  
Ramchander Merugu ◽  
Swetha Garimella ◽  
Laxminarayana E
Keyword(s):  
Biological Activities ◽  
Biologically Active ◽  
Biological Applications ◽  
Essential Component ◽  
Wide Range ◽  
Synthetic Methodologies ◽  
New Compounds

Chromones group of compounds and their derivatives form the essential component of pharmacophores in many biologically active molecules. They exhibit a wide range of biological activities such as antibiotic, antitumor, antiviral, antioxidant, antipsychotic, and antihypoxic activities. These applications have stimulated a continuous search for the synthesis of new compounds in this field and are being extensively investigated. The various methodologies so far reported for the synthesis of these compounds with the compounds biological applications are discussed in this communication

Pharmacokinetics of Dermatan Sulfate in the Rabbit After Intravenous Injection

1988 ◽  
Vol 59 (02) ◽  
pp. 255-258 ◽  
Author(s):  
F Dol ◽  
G Houin ◽  
D Dupouy ◽  
Y Cadroy ◽  
C Caranobe ◽  
...  
Keyword(s):  
Biological Activity ◽  
Low Molecular Weight Heparin ◽  
Dermatan Sulfate ◽  
Biological Activities ◽  
Pharmacokinetic Profile ◽  
Volume Of Distribution ◽  
Low Molecular Weight ◽  
Antithrombotic Agent ◽  
Heparin Cofactor Ii ◽  
Pharmacokinetic Properties

SummaryTo investigate the pharmacokinetic properties of dermatan sulfate (DS), a new potential antithrombotic agent, two different approaches were used. In the first one, DS was derivatized with 3-4 hydroxyphenyl propionic acid N hydroxysuccinimide ester (SHPP) and iodinated. The labelled derivative was injected by IV route to rabbits with increasing doses of unlabelled compound ranging from 20 to 4000 μg/kg. The disappearance of DS from plasma was characterized by measuring both the circulating radioactivity and the biological activity using an original assay based upon the catalysis of heparin cofactor II – thrombin formation. The radioactivity data indicated that the volume of distribution, the clearance and the half life of the tracer were independent of the dose of DS injected. DS concentrations measured by the bioassay indicated that more than 90% were cleared with half lives close to those calculated from the radioactivity data; the remaining biological activity was cleared at a slower rate. Experiments performed with bi-nephrectomized animals indicated that the kidneys play a major role in the elimination of DS or of its metabolites which may have a residual biological activity. In the second set of experiments, unlabelled DS was delivered under continuous intravenous infusion for 5 hours at 5 increasing doses ranging from 160 to 4200 μg/kg/h. The biological activities were used to measure the plateau concentration of DS: there was a linear relationship between the dose delivered and the plasma concentration. These data indicate that the pharmacokinetic profile of DS is very close to that of low molecular weight heparin, and quite different from that of SH.

scholarly journals Synthetic Compounds with 2-Amino-1,3,4-Thiadiazole Moiety Against Viral Infections

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 942 ◽  
Author(s):  
Georgeta Serban
Keyword(s):  
Viral Infections ◽  
Antiviral Agents ◽  
Antiviral Drugs ◽  
Pharmacological Profile ◽  
Synthetic Compounds ◽  
Highly Active ◽  
Pharmacokinetic Properties ◽  
Thiadiazole Derivatives ◽  
Global Threat ◽  
Effective Medication

Viral infections have resulted in millions of victims in human history. Although great efforts have been made to find effective medication, there are still no drugs that truly cure viral infections. There are currently approximately 90 drugs approved for the treatment of human viral infections. As resistance toward available antiviral drugs has become a global threat to health, there is an intrinsic need to identify new scaffolds that are useful in discovering innovative, less toxic and highly active antiviral agents. 1,3,4-Thiadiazole derivatives have been extensively studied due to their pharmacological profile, physicochemical and pharmacokinetic properties. This review provides an overview of the various synthetic compounds containing the 2-amino-1,3,4-thiadiazole moiety that has been evaluated for antiviral activity against several viral strains and could be considered possible prototypes for the development of new antiviral drugs.

scholarly journals A Brief Overview of Potential Treatments for Viral Diseases Using Natural Plant Compounds: The Case of SARS-Cov

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3868
Author(s):  
Rambod Abiri ◽  
Hazandy Abdul-Hamid ◽  
Oksana Sytar ◽  
Ramin Abiri ◽  
Eduardo Bezerra de Almeida ◽  
...  
Keyword(s):  
Viral Infections ◽  
Antiviral Agents ◽  
Herbal Medicines ◽  
Docking Studies ◽  
Biologically Active ◽  
Viral Diseases ◽  
In Vitro Production ◽  
Treatment And Prevention ◽  
Plant Compounds

The COVID-19 pandemic, as well as the more general global increase in viral diseases, has led researchers to look to the plant kingdom as a potential source for antiviral compounds. Since ancient times, herbal medicines have been extensively applied in the treatment and prevention of various infectious diseases in different traditional systems. The purpose of this review is to highlight the potential antiviral activity of plant compounds as effective and reliable agents against viral infections, especially by viruses from the coronavirus group. Various antiviral mechanisms shown by crude plant extracts and plant-derived bioactive compounds are discussed. The understanding of the action mechanisms of complex plant extract and isolated plant-derived compounds will help pave the way towards the combat of this life-threatening disease. Further, molecular docking studies, in silico analyses of extracted compounds, and future prospects are included. The in vitro production of antiviral chemical compounds from plants using molecular pharming is also considered. Notably, hairy root cultures represent a promising and sustainable way to obtain a range of biologically active compounds that may be applied in the development of novel antiviral agents.

scholarly journals Viral Infections in HSCT: Detection, Monitoring, Clinical Management, and Immunologic Implications

2021 ◽  
Vol 11 ◽  
Author(s):  
Claudio Annaloro ◽  
Fabio Serpenti ◽  
Giorgia Saporiti ◽  
Giulia Galassi ◽  
Francesca Cavallaro ◽  
...  
Keyword(s):  
Viral Infections ◽  
Antiviral Agents ◽  
Underlying Disease ◽  
The Other ◽  
Optimal Management ◽  
Dna Viruses ◽  
Hematopoietic Stem ◽  
Limited Effectiveness ◽  
Per Se

In spite of an increasing array of investigations, the relationships between viral infections and allogeneic hematopoietic stem cell transplantation (HSCT) are still controversial, and almost exclusively regard DNA viruses. Viral infections per se account for a considerable risk of morbidity and mortality among HSCT recipients, and available antiviral agents have proven to be of limited effectiveness. Therefore, an optimal management of viral infection represents a key point in HSCT strategies. On the other hand, viruses bear the potential of shaping immunologic recovery after HSCT, possibly interfering with control of the underlying disease and graft-versus-host disease (GvHD), and eventually with HSCT outcome. Moreover, preliminary data are available about the possible role of some virome components as markers of immunologic recovery after HSCT. Lastly, HSCT may exert an immunotherapeutic effect against some viral infections, notably HIV and HTLV-1, and has been considered as an eradicating approach in these indications.

Biologically Active 2,5-Disubstituted-1,3,4-Oxadiazoles

2009 ◽  
Vol 2 (1) ◽  
pp. 390-406
Author(s):  
Harish Rajak ◽  
Murli Dhar Kharya ◽  
Pradeep Mishra
Keyword(s):  
Heterocyclic Compounds ◽  
Medical Literature ◽  
Biological Activities ◽  
Biologically Active ◽  
Pharmacological Properties ◽  
Clinical Use ◽  
Synthetic Drugs ◽  
Physiologic Activity ◽  
Pharmacologically Active

There are vast numbers of pharmacologically active heterocyclic compounds in regular clinical use. The presence of heterocyclic structures in diverse types of compounds is strongly indicative of the profound effects such structure exerts on physiologic activity, and recognition of this is abundantly reflected in efforts to find useful synthetic drugs. The 1,3,4-oxadiazole nucleus has emerged as one of the potential pharmacophore responsible for diverse pharmacological properties. Medical Literature is flooded with reports of a variety of biological activities of 2,5-Disubstituted-1,3,4-oxadiazoles. The present work is an attempt to summarize and enlist the various reports published on biologically active 2,5-disubstituted-1,3,4-oxadiazoles.

Metabolomics of Healthy Berry Fruits

2019 ◽  
Vol 25 (37) ◽  
pp. 4888-4902 ◽  
Author(s):  
Gilda D'Urso ◽  
Sonia Piacente ◽  
Cosimo Pizza ◽  
Paola Montoro
Keyword(s):  
Biological Activities ◽  
Biologically Active ◽  
In Vivo Studies ◽  
Bioactive Metabolites ◽  
Active Metabolites ◽  
Positive Effects ◽  
Cell Functions ◽  
Berry Fruits

The consumption of berry-type fruits has become very popular in recent years because of their positive effects on human health. Berries are in fact widely known for their health-promoting benefits, including prevention of chronic disease, cardiovascular disease and cancer. Berries are a rich source of bioactive metabolites, such as vitamins, minerals, and phenolic compounds, mainly anthocyanins. Numerous in vitro and in vivo studies recognized the health effects of berries and their function as bioactive modulators of various cell functions associated with oxidative stress. Plants have one of the largest metabolome databases, with over 1200 papers on plant metabolomics published only in the last decade. Mass spectrometry (MS) and NMR (Nuclear Magnetic Resonance) are the most important analytical technologies on which the emerging ''omics'' approaches are based. They may provide detection and quantization of thousands of biologically active metabolites from a tissue, working in a ''global'' or ''targeted'' manner, down to ultra-trace levels. In the present review, we highlighted the use of MS and NMR-based strategies and Multivariate Data Analysis for the valorization of berries known for their biological activities, important as food and often used in the preparation of nutraceutical formulations.

Exploring siRNA Umpired Nanogels: A Tale of Barrier Combating Carrier

2020 ◽  
Vol 26 (27) ◽  
pp. 3234-3250
Author(s):  
Sushil K. Kashaw ◽  
Prashant Sahu ◽  
Vaibhav Rajoriya ◽  
Pradeep Jana ◽  
Varsha Kashaw ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Biomedical Engineering ◽  
Viral Infections ◽  
Slow Release ◽  
Molecular Level ◽  
Release Kinetics ◽  
Biologically Active ◽  
Release Process ◽  
Rapid Release ◽  
Wide Range

Potential short interfering RNAs (siRNA) modulating gene expression have emerged as a novel therapeutic arsenal against a wide range of maladies and disorders containing cancer, viral infections, bacterial ailments and metabolic snags at the molecular level. Nanogel, in the current medicinal era, displayed a comprehensive range of significant drug delivery prospects. Biodegradation, swelling and de-swelling tendency, pHsensitive drug release and thermo-sensitivity are some of the renowned associated benefits of nanogel drug delivery system. Global researches have also showed that nanogel system significantly targets and delivers the biomolecules including DNAs, siRNA, protein, peptides and other biologically active molecules. Biomolecules delivery via nanogel system explored a wide range of pharmaceutical, biomedical engineering and agro-medicinal application. The siRNAs and DNAs delivery plays a vivacious role by addressing the hitches allied with chronic and contemporary therapeutic like generic possession and low constancy. They also incite release kinetics approach from slow-release while mingling to rapid release at the targets will be beneficial as interference RNAs delivery carriers. Therefore, in this research, we focused on the latest improvements in the delivery of siRNA loaded nanogels by enhancing the absorption, stability, sensitivity and combating the hindrances in cellular trafficking and release process.

Synthetic Routes for 1,4-disubstituted 1,2,3-triazoles: A Review

2019 ◽  
Vol 23 (8) ◽  
pp. 860-900 ◽  
Author(s):  
Chander P. Kaushik ◽  
Jyoti Sangwan ◽  
Raj Luxmi ◽  
Krishan Kumar ◽  
Ashima Pahwa
Keyword(s):  
Solid Phase ◽  
Click Reaction ◽  
Biological Activities ◽  
Triazole Ring ◽  
Copper Catalysts ◽  
Biologically Active ◽  
Pharmaceutical Chemistry ◽  
Biological Targets ◽  
Synthetic Routes ◽  
High Yields

N-Heterocyclic compounds like 1,2,3-triazoles serve as a key scaffolds among organic compounds having diverse applications in the field of drug discovery, bioconjugation, material science, liquid crystals, pharmaceutical chemistry and solid phase organic synthesis. Various drugs containing 1,2,3-triazole ring which are commonly available in market includes Rufinamide, Cefatrizine, Tazobactam etc., Stability to acidic/basic hydrolysis along with significant dipole moment support triazole moiety for appreciable participation in hydrogen bonding and dipole-dipole interactions with biological targets. Huisgen 1,3-dipolar azide-alkyne cycloaddition culminate into a mixture of 1,4 and 1,5- disubstituted 1,2,3-triazoles. In 2001, Sharpless and Meldal came across with a copper(I) catalyzed regioselective synthesis of 1,4-disubstituted 1,2,3-triazoles by cycloaddition between azides and terminal alkynes. This azide-alkyne cycloaddition has been labelled as a one of the important key click reaction. Click synthesis describes chemical reactions that are simple to perform, gives high selectivity, wide in scope, fast reaction rate and high yields. Click reactions are not single specific reaction, but serve as a pathway for construction of simple to complex molecules from a variety of starting materials. In the last few decades, 1,2,3-triazoles attracted attention of researchers all over the world because of their broad spectrum of biological activities. Keeping in view the biological importance of 1,2,3-triazole, in this review we focus on the various synthetic routes for the syntheisis of 1,4-disubstituted 1,2,3-triazoles. This review involves various synthetic protocols which involves copper and non-copper catalysts, different solvents as well as substrates. It will boost synthetic chemists to explore new pathway for the development of newer biologically active 1,2,3-triazoles.

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