The Efficiency of Multi-target Drugs: A Network Approach

Alberca, Lucas Nicolás; Talevi, Alan

doi:10.1007/978-3-030-32857-3_3

Cited by 3 publications

(1 citation statement)

References 62 publications

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“…One of the strategies for designing multitarget ligands is to integrate two or more pharmacophoric fragments in one molecule [ 18 ]. Therefore, the design of a multitarget drug for a complex disease should begin with selecting appropriate targets, using some strategies like high-throughput screening or network pharmacology [ 19 ], although this is not always an easy task [ 20 ]. Several studies have found that the dysregulation in the mechanisms of some enzymes and receptors is related to the physiopathology and complications of MetS.…”

Section: Introductionmentioning

confidence: 99%

In Silico-Based Design and In Vivo Evaluation of an Anthranilic Acid Derivative as a Multitarget Drug in a Diet-Induced Metabolic Syndrome Model

et al. 2021

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Metabolic syndrome (MetS) is a complex disease that affects almost a quarter of the world’s adult population. In MetS, diabetes, obesity, hyperglycemia, high cholesterol, and high blood pressure are the most common disorders. Polypharmacy is the most used strategy for managing conditions related to MetS, but it has drawbacks such as low medication adherence. Multitarget ligands have been proposed as an interesting approach to developing drugs to treat complex diseases. However, suitable preclinical models that allow their evaluation in a context closer to a clinical situation of a complex disease are needed. From molecular docking studies, compound 1b, a 5-aminoanthranilic acid derivative substituted with 4′-trifluoromethylbenzylamino and 3′,4′-dimethoxybenzamide moieties, was identified as a potential multitarget drug, as it showed high in silico affinity against targets related to MetS, including PPAR-α, PPAR-γ, and HMG-CoA reductase. It was evaluated in a diet-induced MetS rat model and simultaneously lowered blood pressure, glucose, total cholesterol, and triglyceride levels after a 14-day treatment. No toxicity events were observed during an acute lethal dose evaluation test at 1500 mg/kg. Hence, the diet-induced MetS model is suitable for evaluating treatments for MetS, and compound 1b is an attractive starting point for developing multitarget drugs.

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Section: Introductionmentioning

confidence: 99%

In Silico-Based Design and In Vivo Evaluation of an Anthranilic Acid Derivative as a Multitarget Drug in a Diet-Induced Metabolic Syndrome Model

et al. 2021

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Drugs from drugs: New chemical insights into a mature concept

Baró,

Catti,

Estarellas

et al. 2024

Drug Discovery Today

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“Golden Shot” in the Treatment and Diagnosis of Schizophrenia: Psychiatrists or Neuroscientists?

Dubatova

Antsyborov

Kheigetian

et al. 2021

ISci

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The available published data indicate that antagonism towards D2 receptors of dopamine is a «necessary condition» in the process of effective treatment of schizophrenia, but at the same time, this antagonism is insufficient to achieve a state of complete remission. These data serve as a powerful stimulus for the process of searching new treatments and synthesizing new drugs. The current status of the theory of neural networks demonstrates to the professional community that in order to effectively change the functioning of basic biological systems, a number of subtle changes in the central nervous system are required, which are possible with the use of certain substances. The influence of modulation of glutamate on these processes is currently a very «popular» direction both in neurobiology and in clinical psychiatry. At the same time, the role of the latter in the pathogenesis of a number of mental disorders remains unproven. In parallel with this direction, the mechanisms of serotonergic and cholinergic effects on the main components of the pathogenesis of mental disorders are being studied and used in the development of new antipsychotic drugs. Most antipsychotic drugs which belong to «new wave» exhibit an affinity for different types of receptors, which mediate the effect on several therapeutic targets. In practice, a large number of patients take certain drugs not only as monotherapy, but often combine them with other drugs. At the same time, the effectiveness of such therapeutical regimens is low. Therefore, in most modern protocols, monotherapy is still recommended. In recent years, there has been a growing body of research on pharmacotherapy augmentation strategies. The results of these studies demonstrate that augmentation preparations belonging to different pharmacological classes can be generally effective, not only in certain diseases, but also in certain types of patients. In attempts to create a model of «rational polypharmacy», it is very important to accurately define and target the therapy to «problematic symptoms», and it is also necessary to develop an optimal withdrawal strategy from the active therapy regimen. To date, the only existing «lifeline» is Clozapine, which, despite its many disadvantages, remains an effective therapeutic agent for resistant forms of schizophrenic spectrum disorders. New methods of drug synthesis, including «individual drug affinity» analysis and strategies based on the study of gene polymorphism, look promising in the context of antipsychotic drug development. It is unlikely that there will be a «golden shot» for the schizophrenic spectrum disorders in the coming decades, both in terms of diagnostics and treatment. There is a hope that some of the strategies currently being developed (polypharmacy, augmentation), along with new antipsychotic drugs entering the pharmaceutical market, will ultimately become the «shot» that the professional community, patients and their families are looking forward to.

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The Efficiency of Multi-target Drugs: A Network Approach

Cited by 3 publications

References 62 publications

In Silico-Based Design and In Vivo Evaluation of an Anthranilic Acid Derivative as a Multitarget Drug in a Diet-Induced Metabolic Syndrome Model

In Silico-Based Design and In Vivo Evaluation of an Anthranilic Acid Derivative as a Multitarget Drug in a Diet-Induced Metabolic Syndrome Model

Drugs from drugs: New chemical insights into a mature concept

“Golden Shot” in the Treatment and Diagnosis of Schizophrenia: Psychiatrists or Neuroscientists?

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