Literature DB >> 29439902

MF-8, a novel promising arylpiperazine-hydantoin based 5-HT7 receptor antagonist: In vitro drug-likeness studies and in vivo pharmacological evaluation.

Gniewomir Latacz1, Annamaria Lubelska2, Magdalena Jastrzębska-Więsek3, Anna Partyka3, Katarzyna Kucwaj-Brysz2, Anna Wesołowska3, Katarzyna Kieć-Kononowicz2, Jadwiga Handzlik4.   

Abstract

We report the in vitro drug-likeness studies and in vivo pharmacological evaluation for a new potent 5-HT7 receptor antagonist MF-8 (5-(4-fluorophenyl)-3-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl)-5-methylhydantoin). The in vitro tests showed good permeability, very good metabolic stability, low risk of drug-drug interactions and satisfying safety profile. Moreover, MF-8 showed excellent antidepressant-like activity in the forced swim test in rodents and promising anxiolytic-like activity in the four-plate test in mice. Regarding the potent affinity, high selectivity and antagonistic activity of MF-8 for the 5-HT7 receptor as well as excellent drug - like properties in vitro and confirmed in vivo pharmacological activity, MF-8 should be considered as a very significant molecule in the search for a new class of anti-depressant drugs.
Copyright © 2018 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  5-HT7 receptor antagonist; Antidepressant-like activity; Anxiolytic-like activity; Arylpiperazines; Drug-like properties

Mesh:

Substances:

Year:  2018        PMID: 29439902     DOI: 10.1016/j.bmcl.2018.02.003

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN: 0960-894X            Impact factor:   2.823


  4 in total

1.  The role of aryl-topology in balancing between selective and dual 5-HT7R/5-HT1A actions of 3,5-substituted hydantoins.

Authors:  Katarzyna Kucwaj-Brysz; Rafał Kurczab; Ewa Żesławska; Annamaria Lubelska; Małgorzata Anna Marć; Gniewomir Latacz; Grzegorz Satała; Wojciech Nitek; Katarzyna Kieć-Kononowicz; Jadwiga Handzlik
Journal:  Medchemcomm       Date:  2018-05-08       Impact factor: 3.597

2.  Search for ABCB1 Modulators Among 2-Amine-5-Arylideneimidazolones as a New Perspective to Overcome Cancer Multidrug Resistance.

Authors:  Aneta Kaczor; Márta Nové; Annamária Kincses; Gabriella Spengler; Ewa Szymańska; Gniewomir Latacz; Jadwiga Handzlik
Journal:  Molecules       Date:  2020-05-11       Impact factor: 4.411

3.  Are the Hydantoin-1,3,5-triazine 5-HT6R Ligands a Hope to a Find New Procognitive and Anti-Obesity Drug? Considerations Based on Primary In Vivo Assays and ADME-Tox Profile In Vitro.

Authors:  Annamaria Lubelska; Gniewomir Latacz; Magdalena Jastrzębska-Więsek; Magdalena Kotańska; Rafał Kurczab; Anna Partyka; Małgorzata Anna Marć; Daria Wilczyńska; Agata Doroz-Płonka; Dorota Łażewska; Anna Wesołowska; Katarzyna Kieć-Kononowicz; Jadwiga Handzlik
Journal:  Molecules       Date:  2019-12-06       Impact factor: 4.411

4.  Discovery of Novel pERK1/2- or β-Arrestin-Preferring 5-HT1A Receptor-Biased Agonists: Diversified Therapeutic-like versus Side Effect Profile.

Authors:  Joanna Sniecikowska; Monika Gluch-Lutwin; Adam Bucki; Anna Więckowska; Agata Siwek; Magdalena Jastrzebska-Wiesek; Anna Partyka; Daria Wilczyńska; Karolina Pytka; Gniewomir Latacz; Katarzyna Przejczowska-Pomierny; Elżbieta Wyska; Anna Wesołowska; Maciej Pawłowski; Adrian Newman-Tancredi; Marcin Kolaczkowski
Journal:  J Med Chem       Date:  2020-09-23       Impact factor: 7.446

  4 in total

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