Literature DB >> 31724859

New Dual Small Molecules for Alzheimer's Disease Therapy Combining Histamine H3 Receptor (H3R) Antagonism and Calcium Channels Blockade with Additional Cholinesterase Inhibition.

Rim Malek1,2, Raquel L Arribas3,4, Alejandra Palomino-Antolin4,5,6, Perle Totoson7, Celine Demougeot7, Tereza Kobrlova8,9, Ondrej Soukup8,9, Isabel Iriepa, Ignacio Moraleda, Daniel Diez-Iriepa10, Justyna Godyń11, Dawid Panek11, Barbara Malawska11, Monika Głuch-Lutwin11, Barbara Mordyl11, Agata Siwek11, Fakher Chabchoub2, José Marco-Contelles10, Katarzyna Kiec-Kononowicz11, Javier Egea4,5,6, Cristóbal de Los Ríos3,4, Lhassane Ismaili1.   

Abstract

New tritarget small molecules combining Ca2+ channels blockade, cholinesterase, and H3 receptor inhibition were obtained by multicomponent synthesis. Compound 3p has been identified as a very promising lead, showing good Ca2+ channels blockade activity (IC50 = 21 ± 1 μM), potent affinity against hH3R (Ki = 565 ± 62 nM), a moderate but selective hBuChE inhibition (IC50 = 7.83 ± 0.10 μM), strong antioxidant power (3.6 TE), and ability to restore cognitive impairment induced by lipopolysaccharide.

Entities:  

Year:  2019        PMID： 31724859     DOI： 10.1021/acs.jmedchem.9b00937

Source DB:  PubMed          Journal:  J Med Chem        ISSN： 0022-2623            Impact factor:   7.446


  8 in total

Review 1.  Recent advances in multitarget-directed ligands targeting G-protein-coupled receptors.

Authors:  Hongguang Ma; Boshi Huang; Yan Zhang
Journal:  Drug Discov Today       Date:  2020-07-09       Impact factor: 7.851

2.  Synthesis and molecular modeling studies of cholinesterase inhibitor dispiro[indoline-3,2'-pyrrolidine-3',3''-pyrrolidines].

Authors:  M Adel Youssef; Siva S Panda; Riham A El-Shiekh; ElSayed M Shalaby; Dalia R Aboshouk; Walid Fayad; Nehmedo G Fawzy; Adel S Girgis
Journal:  RSC Adv       Date:  2020-06-08       Impact factor: 4.036

3.  Triazolopyridopyrimidine: A New Scaffold for Dual-Target Small Molecules for Alzheimer's Disease Therapy.

Authors:  Lazhar Zribi; Irene Pachòn-Angona; Òscar M Bautista-Aguilera; Daniel Diez-Iriepa; José Marco-Contelles; Lhassane Ismaili; Isabel Iriepa; Fakher Chabchoub
Journal:  Molecules       Date:  2020-07-13       Impact factor: 4.411

4.  In-silico discovery of dual active molecule to restore synaptic wiring against autism spectrum disorder via HDAC2 and H3R inhibition.

Authors:  Anupam Raja; Nishant Shekhar; Harvinder Singh; Ajay Prakash; Bikash Medhi
Journal:  PLoS One       Date:  2022-07-25       Impact factor: 3.752

5.  Development of spiro-3-indolin-2-one containing compounds of antiproliferative and anti-SARS-CoV-2 properties.

Authors:  Nehmedo G Fawazy; Siva S Panda; Ahmed Mostafa; Benson M Kariuki; Mohamed S Bekheit; Yassmin Moatasim; Omnia Kutkat; Walid Fayad; May A El-Manawaty; Ahmed A F Soliman; Riham A El-Shiekh; Aladdin M Srour; Reham F Barghash; Adel S Girgis
Journal:  Sci Rep       Date:  2022-08-16       Impact factor: 4.996

6.  Design, Synthesis and Biological Evaluation of New Antioxidant and Neuroprotective Multitarget Directed Ligands Able to Block Calcium Channels.

Authors:  Irene Pachòn Angona; Solene Daniel; Helene Martin; Alexandre Bonet; Artur Wnorowski; Maciej Maj; Krzysztof Jóźwiak; Tiago Barros Silva; Bernard Refouvelet; Fernanda Borges; José Marco-Contelles; Lhassane Ismaili
Journal:  Molecules       Date:  2020-03-14       Impact factor: 4.411

7.  Synthesis of Hantzsch Adducts as Cholinesterases and Calcium Flux inhibitors, Antioxidants and Neuroprotectives.

Authors:  Irene Pachón Angona; Helene Martin; Solene Daniel; Ignacio Moraleda; Alexandre Bonet; Artur Wnorowski; Maciej Maj; Krzysztof Jozwiak; Isabel Iriepa; Bernard Refouvelet; José Marco-Contelles; Lhassane Ismaili
Journal:  Int J Mol Sci       Date:  2020-10-16       Impact factor: 5.923

8.  Multidirectional in vitro and in cellulo studies as a tool for identification of multi-target-directed ligands aiming at symptoms and causes of Alzheimer's disease.

Authors:  Natalia Szałaj; Justyna Godyń; Jakub Jończyk; Anna Pasieka; Dawid Panek; Tomasz Wichur; Krzysztof Więckowski; Paula Zaręba; Marek Bajda; Anja Pislar; Barbara Malawska; Raimon Sabate; Anna Więckowska
Journal:  J Enzyme Inhib Med Chem       Date:  2020-12       Impact factor: 5.051
  8 in total

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