Design and Properties of New Multi-target Michael Acceptors

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F24%3A00137891" target="_blank" >RIV/00216224:14110/24:00137891 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.33542/NTI-0370-8" target="_blank" >http://dx.doi.org/10.33542/NTI-0370-8</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.33542/NTI-0370-8" target="_blank" >10.33542/NTI-0370-8</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Design and Properties of New Multi-target Michael Acceptors

Popis výsledku v původním jazyce

Increasing microbial burden and the development of antimicrobial resistance (AMR) pose a major threat to human health worldwide. In addition to the increased risk of patient death, AMR represents a longer hospital stay and increased health care costs. This state of affairs is extremely undesirable and, apart from various approaches , it is of course most advantageous to design new entities with a new/innovative mechanism of action. One possibility for the design of new drugs is inspiration from natural compounds with multiple activities. Our team specializes in the investigations of multi-target anti-invasive agents based on ring-substituted azanaphthalene bioisosteres; such as hydroxynaphthanilides with activity against Gram-positive bacteria and mycobacteria. Modifications to increase solubility led to the removal of one ring, resulting in the (E)-prop-1-en-1-ylbenzene scaffold. A number of different ring-substituted anilides were designed, prepared and tested. Moieties with electron-withdrawing properties were chosen as substituents of the anilide ring. These designed agents meet the definition of so-called Michael acceptors, i.e. compounds in which double/triple bonds are conjugated with electron-withdrawing groups and which are able to react with nucleophiles, i.e., electron-rich substrates, and thus have the ability to interact with many biological targets. This contribution focuses on the design, biological investigations and discussion of structure-activity relationships within several series of new amides.

Název v anglickém jazyce

Design and Properties of New Multi-target Michael Acceptors

Popis výsledku anglicky

Increasing microbial burden and the development of antimicrobial resistance (AMR) pose a major threat to human health worldwide. In addition to the increased risk of patient death, AMR represents a longer hospital stay and increased health care costs. This state of affairs is extremely undesirable and, apart from various approaches , it is of course most advantageous to design new entities with a new/innovative mechanism of action. One possibility for the design of new drugs is inspiration from natural compounds with multiple activities. Our team specializes in the investigations of multi-target anti-invasive agents based on ring-substituted azanaphthalene bioisosteres; such as hydroxynaphthanilides with activity against Gram-positive bacteria and mycobacteria. Modifications to increase solubility led to the removal of one ring, resulting in the (E)-prop-1-en-1-ylbenzene scaffold. A number of different ring-substituted anilides were designed, prepared and tested. Moieties with electron-withdrawing properties were chosen as substituents of the anilide ring. These designed agents meet the definition of so-called Michael acceptors, i.e. compounds in which double/triple bonds are conjugated with electron-withdrawing groups and which are able to react with nucleophiles, i.e., electron-rich substrates, and thus have the ability to interact with many biological targets. This contribution focuses on the design, biological investigations and discussion of structure-activity relationships within several series of new amides.

Druh

O - Ostatní výsledky

CEP obor

—

OECD FORD obor

30107 - Medicinal chemistry

Projekt

—

Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů