Advances in the application of 1,2,4-triazole-containing hybrids as anti-tuberculosis agents

2021 ◽  
Author(s):  
Yingdong Cao ◽  
Hong Lu
Keyword(s):  
Side Effects ◽  
Rational Design ◽  
Communicable Disease ◽  
Mechanisms Of Action ◽  
New Drugs ◽  
Current Status ◽  
Potential Drug ◽  
Antitubercular Agents ◽  
Drug Candidates ◽  
Privileged Structure

Tuberculosis is a deadly communicable disease caused by the bacillus Mycobacterium tuberculosis (MTB), and pulmonary tuberculosis accounts for over 80% of the total cases. The 1,2,4-triazole is a privileged structure in the discovery of new drugs, and its derivatives act on various targets in MTB. In particular, 1,2,4-triazole hybrids can not only exert dual or multiple antitubercular mechanisms of action but also have the potential to enhance efficacy and reduce side effects. The present work aims to summarize the current status of 1,2,4-triazole hybrids as potential antitubercular agents, covering articles published between 2010 and 2020, to aid the further rational design of novel potential drug candidates endowed with higher efficacy, better compliance and fewer side effects.

Recent Advances in the Development of Antimicrobial Peptides (AMPs): Attempts for Sustainable Medicine?

2018 ◽  
Vol 25 (21) ◽  
pp. 2503-2519 ◽  
Author(s):  
Anne Kokel ◽  
Marianna Torok
Keyword(s):  
Side Effects ◽  
Antimicrobial Peptides ◽  
Potential Drug ◽  
Green Technologies ◽  
Specific Antibodies ◽  
Structural Modifications ◽  
Drug Candidates ◽  
Induce Resistance ◽  
Conventional Antibiotics

Background: Since the first isolation of antimicrobial peptides (AMPs) they have attracted extensive interest in medicinal chemistry. However, only a few AMP-based drugs are currently available on the market. Despite their effectiveness, biodegradability, and versatile mode of action that is less likely to induce resistance compared to conventional antibiotics, AMPs suffer from major issues that need to be addressed to broaden their use. Notably, AMPs can lack selectivity leading to side effects and cytotoxicity, and also exhibit in vivo instability. Several strategies are being actively considered to overcome the limitations that restrain the success of AMPs. Methods: In the current work, recent strategies reported for improving AMPs in the context of drug design and delivery were surveyed, and also their possible impact on patients and the environment was assessed. Results: As a major advantage AMPs possess an easily tunable skeleton offering opportunities to improve their properties. Strategic structural modifications and the beneficial properties of cyclic or branched AMPs in term of stability have been reported. The conjugation of AMPs with nanoparticles has also been explored to increase their in vivo stability. Other techniques such as the coupling of AMPs with specific antibodies aim to increase the selectivity of the potential drug towards the target. These strategies were evaluated for their effect on the environment highlighting green technologies. Conclusion: Although further research is needed taking into account both environmental and human health consequences of novel AMPs, several of these compounds are promising drug candidates for use in sustainable medicine.

scholarly journals Monotherapy or Polytherapy for Epilepsy?

1998 ◽  
Vol 25 (S4) ◽  
pp. S3-S8 ◽  
Author(s):  
Alan Guberman
Keyword(s):  
Side Effects ◽  
Seizure Control ◽  
Lower Cost ◽  
Mechanisms Of Action ◽  
New Drugs ◽  
First Line ◽  
New Antiepileptic Drugs ◽  
Epilepsy Treatment ◽  
Multiple Drugs ◽  
The Ideal

ABSTRACT:Monotherapy has been promoted as the ideal in epilepsy treatment because of reduced side effects, absence of drug interactions, better compliance, lower cost and, in many cases, improved seizure control compared to polytherapy. The question of monotherapy vs. polytherapy has assumed increasing importance with the availability of multiple new antiepileptic drugs (AEDs), initially tested as add-on agents. The new drugs clobazam, lamotrigine, vigabatrin, gabapentin and topiramate, have also been shown to be effective as monotherapy. These data bring up the possibility of using them as first-line agents. However, a high percentage of patients with resistant epilepsy are treated with polytherapy, which probably benefits only a minority of them. The availability of multiple drugs with different mechanisms of action favours the possibility of "rational polytherapy", taking advantage of possible synergism, a yet unproven concept. This article reviews the theoretical advantages of monotherapy and monotherapy with traditional and newer AEDs.

scholarly journals Inter-individual variability and modeling of electrical activity: a possible new approach to explore cardiac safety?

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Jean-Yves Le Guennec ◽  
Jérôme Thireau ◽  
Aude Ouillé ◽  
Julien Roussel ◽  
Jérôme Roy ◽  
...  
Keyword(s):  
Side Effects ◽  
Computational Models ◽  
Simulation Models ◽  
Human Action ◽  
Individual Variability ◽  
New Drugs ◽  
Channel Blockers ◽  
Nucleotide Polymorphisms ◽  
Cardiac Side Effects ◽  
Drug Candidates

Abstract Safety pharmacology aims to predict rare side effects of new drugs. We explored whether rare pro-arrhythmic effects could be linked to the variability of the effects of these drugs on ion currents and whether taking into consideration this variability in computational models could help to better detect and predict cardiac side effects. For this purpose, we evaluated how intra- and inter-individual variability influences the effect of hERG inhibition on both the action potential duration and the occurrence of arrhythmias. Using two computer simulation models of human action potentials (endocardial and Purkinje cells), we analyzed the contribution of two biological parameters on the pro-arrhythmic effects of several hERG channel blockers: (i) spermine concentration, which varies with metabolic status, and (ii) L-type calcium conductance, which varies due to single nucleotide polymorphisms or mutations. By varying these parameters, we were able to induce arrhythmias in 1 out of 16 simulations although conventional modeling methods to detect pro-arrhythmic molecules failed. On the basis of our results, taking into consideration only 2 parameters subjected to intra- and inter-individual variability, we propose that in silico computer modeling may help to better define the risks of new drug candidates at early stages of pre-clinical development.

scholarly journals Review of properties and mechanisms of action of hepatoprotective drugs

2020 ◽  
pp. 36-44
Author(s):  
Е.В. Кардаш ◽  
Е.М. Григорьева ◽  
А.Г. Емельянова ◽  
С.А. Тарасов
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Side Effects ◽  
Randomized Clinical Trials ◽  
Evidence Base ◽  
Mechanisms Of Action ◽  
New Drugs ◽  
Simultaneous Administration ◽  
Essential Phospholipids ◽  
Meta Analyses

В медицинской практике достаточно часто возникает необходимость в одновременном приеме нескольких лекарственных средств. Иногда это оказывается невозможным в силу наличия у препаратов гепатотоксических свойств, поэтому актуальными задачами фармакологии являются как поиск и разработка новых препаратов, так и оптимизация уже существующих с целью уменьшения побочных эффектов при их приеме. В настоящем обзоре были проанализированы данные о фармакологических препаратах класса гепатопротекторов, разобраны механизмы их действия и потенциал поиска новых препаратов. В заключение отмечено, что в настоящее время в клинической практике наибольшей популярностью пользуются препараты, содержащие эссенциальные фосфолипиды и препараты, улучшающие рециркуляцию и выведение желчных кислот. Существуют теоретические обоснования механизмов действия этих препаратов и перспектива накопления доказательной базы для них в виде рандомизированных клинических исследований и мета-анализов. Medical practice quite often requires simultaneous administration of several drugs. Sometimes it is impossible due to their hepatotoxicity; therefore, urgent tasks of pharmacology include searching for and developing new drugs as well as optimizing already existing products in order to reduce side effects during their administration. This review focused on pharmacological drugs of the hepatoprotector class and their mechanisms of action and evaluated the prospects of searching for new medicines. In conclusion, drugs containing essential phospholipids and those improving recirculation and removal of bile acids are currently the most popular agents in clinical practice. Mechanisms of action of these drugs are theoretically justified and there is a prospect for building an evidence base for them by randomized clinical trials and meta-analyses.

scholarly journals New drugs in psychiatry: focus on new pharmacological targets

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 397 ◽  
Author(s):  
Filippo Caraci ◽  
Gian Marco Leggio ◽  
Salvatore Salomone ◽  
Filippo Drago
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cannabinoid Receptors ◽  
Mechanisms Of Action ◽  
New Drugs ◽  
Progressive Decline ◽  
Drug Candidates ◽  
Pharmacological Targets ◽  
Treatment Of Depression ◽  
Dopamine D3

The approval of psychotropic drugs with novel mechanisms of action has been rare in recent years. To address this issue, further analysis of the pathophysiology of neuropsychiatric disorders is essential for identifying new pharmacological targets for psychotropic medications. In this report, we detail drug candidates being examined as treatments for psychiatric disorders. Particular emphasis is placed on agents with novel mechanisms of action that are being tested as therapies for depression, schizophrenia, or Alzheimer’s disease. All of the compounds considered were recently approved for human use or are in advanced clinical trials. Drugs included here are new antipsychotic medications endowed with a preferential affinity at dopamine D3 receptor (cariprazine) or at glutamatergic or cannabinoid receptors, as well as vortioxetine, a drug approved for managing the cognitive deficits associated with major depression. New mechanistic approaches for the treatment of depression include intravenous ketamine or esketamine or intranasal esketamine. As for Alzheimer’s disease, the possible value of passive immunotherapy with agents such as aducanumab is considered to be a potential disease-modifying approach that could slow or halt the progressive decline associated with this devastating disorder.

Antipicornavirus Drugs: Current Status

1997 ◽  
Vol 8 (5) ◽  
pp. 401-408 ◽  
Author(s):  
GD Diana ◽  
DC Pevear
Keyword(s):  
Crystal Structure ◽  
Broad Spectrum ◽  
Clinical Status ◽  
Current Status ◽  
Potential Drug ◽  
Virus Structure ◽  
X Ray ◽  
Drug Candidates ◽  
The Past ◽  
Made In

Considerable efforts have been made over the past several years to discover a broad-spectrum antipicornavirus agent. The X-ray crystal structure of several rhinovirus serotypes, as well as a coxsackievirus, has provided valuable information with respect to the virus structure as well as the location of the binding site of several capsid-binding compounds. This has aided in the design of broad-spectrum compounds. Several potential drug candidates have reached clinical status and some progress has been made in achieving efficacy. However, none of these compounds has as yet become a marketable drug. This review summarizes the current status of efforts in this area.

scholarly journals The Ethyl Acetate Extraction Obtained from Podocarpus Nagikernel Meal with Anticancer Activity

2021 ◽  
Vol 14 (1) ◽  
pp. 363-366
Author(s):  
Yuchen Xiao ◽  
Jianping Yong ◽  
Yang Yang ◽  
Canzhong Lu
Keyword(s):  
Side Effects ◽  
Anticancer Activity ◽  
Anticancer Drugs ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Public Health Problem ◽  
New Drugs ◽  
Major Public Health Problem ◽  
Drug Candidates

Cancer is a major public health problem worldwide, and it is one of the top three major diseases in terms of mortality. Some small molecular synthesized drugs have been used clinically. However, much side-effects were also appeared during treatment of the cancer patients with the synthesized anticancer drugs in clinical. Some Chinese Traditional Plant Medicines have ever been used for treatment of cancer with the low side-effects. Thus, it is essential to find anticancer drugs or drug candidates from Chinese Traditional Plant Medicines. Podocarpus nagicontains different kinds of biological components together with a wide spectrum of biological activities, and it has ever been used in the folk of Yao Nationality for treatment different diseases. It is essential to study this folk plant medicine to discover new drugs or drug candidates. In this work, we obtained different polar extractions and evaluated their in vitro anticancer activity.

Triazole-containing hybrids with anti-Mycobacterium tuberculosis potential – Part I: 1,2,3-Triazole

2021 ◽  
Author(s):  
Zhenyou Tan ◽  
Jun Deng ◽  
Qiongxian Ye ◽  
Zhenfeng Zhang
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Rational Design ◽  
Multidrug Therapy ◽  
Resistance Development ◽  
Drug Candidates ◽  
Structure Activity ◽  
Privileged Structure ◽  
Potential Part ◽  
Potential Activity

Tuberculosis regimens currently applied in clinical practice require months of multidrug therapy, which imposes a major challenge of patient compliance and drug resistance development. Moreover, because of the increasing emergence of hard-to-treat tuberculosis, this disease continues to be a significant threat to the human population. 1,2,3-triazole as a privileged structure has been widely used as an effective template for drug discovery, and 1,2,3-triazole-containing hybrids that can simultaneously act on dual or multiple targets in Mycobacterium tuberculosis have the potential to circumvent drug resistance, enhance efficacy, reduce side effects and improve pharmacokinetic as well as pharmacodynamic profiles. Thus, 1,2,3-triazole-containing hybrids are useful scaffolds for the development of antitubercular agents. This review aims to highlight recent advances of 1,2,3-triazole-containing hybrids with potential activity against various forms of M. tuberculosis, covering articles published between 2015 and 2020. The structure–activity relationship and the mechanism of action are also discussed to facilitate further rational design of more effective drug candidates.

New Trends On Biological Activities And Clinical Studies Of Quinolinic Analogues: A Review

2021 ◽  
Vol 22 ◽  
Author(s):  
Sandra Elizabeth Barbosa da Silva ◽  
José Arion da Silva Moura ◽  
Tiago Rafael de Sousa Nunes ◽  
Ivan da Rocha Pitta ◽  
Marina Galdino da Rocha Pitta
Keyword(s):  
Side Effects ◽  
Clinical Studies ◽  
Biological Activities ◽  
Mechanisms Of Action ◽  
Antimalarial Drugs ◽  
New Drugs ◽  
Phase Iii ◽  
Synthetic Compounds ◽  
Preclinical And Clinical Studies ◽  
Natural And Synthetic

: The quinolinic ring, present in several molecules, has a great diversity of biological activities. Therefore, this ring is in the structure composition of several candidates of drugs in preclinical and clinical studies, thus, it is necessary the grouping of these results to facilitate the design of new drugs. For this reason, some of the activities were selected for this review, such as: antimalarial, antimicrobial, anticancer, anti-inflammatory, antidiabetic, anti-rheumatic and antiviral. All publications of scientific articles chosen are dated between 2000 and 2020. In addition to presenting the structures of some natural and synthetic compounds with their activities, we list the clinical studies of phases III and IV of antimalarial drugs containing the quinoline nucleus and phase III clinical studies of hydroxychloroquine and chloroquine to assess their possible role in COVID-19. Finally, we show some of the mechanisms of action, as well as the side effects of some of the quinolinic derivatives.

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