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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Drug design of new 5-HT6R antagonists aided by artificial neural networks

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Author(s):
da Silva, Aldineia P. [1] ; Chiari, Laise P. A. [1] ; Guimaraes, Amanda R. [1] ; Honorio, Kathia M. [2] ; da Silva, Alberico B. F. [1]
Total Authors: 5
Affiliation:
[1] Univ Sao Paulo, Inst Quim Sao Carlos, Dept Quim & Fis Mol, CP 780, BR-13560970 Sao Carlos, SP - Brazil
[2] Univ Sao Paulo, Escola Artes Ciencia & Humanidades, BR-03828000 Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: JOURNAL OF MOLECULAR GRAPHICS & MODELLING; v. 104, MAY 2021.
Web of Science Citations: 0
Abstract

Alzheimer's Disease (AD) is the most frequent illness and cause of death amongst the age relatedneurodegenerative disorders. The Alzheimer's Disease International (ADI) reported in 2019 that over 50 million people were living with dementia in the world and this number could potentially be around 152 million by 2050.5-hydroxtryptamine subtype 6 receptor (5-HT6R) has been identified as a potential anti-amnesic drug target and therefore, the administration of 5-HT6R antagonists can likely mitigate the memory loss and intellectual deterioration associated with AD. Herein, computational tools were applied to design new 5-HT6 antagonists and their biological activity values were predicted by our QSAR model obtained from Artificial Neural Networks (ANN). The proposed compounds here from the QSAR-ANN model presented significant biological activity values and some of them have achieved pKi above 9.00. Furthermore, our results suggest that the presence of halogen atoms (especially bromine) linked to the aromatic ring at para-position (HYD) contribute considerably to the increase of the biological activity values while bulky groups in the PI position do not culminate with the increase antagonist activity of compounds here analyzed. Finally, the ADME/Tox profile as well as the synthetic accessibility of new proposed compounds qualify them to go on further with experimental procedures and thenceforward their antagonist effects can be confirmed. (C) 2021 Published by Elsevier Inc. (AU)

FAPESP's process: 16/24524-7 - STRUCTURAL ANALYSIS AND MOLECULAR MODELING STUDIES FOR NATURAL AND SYNTHETIC LIGANTS RELATED TO NEGLECTED DISEASES
Grantee:Kathia Maria Honorio
Support Opportunities: Regular Research Grants
FAPESP's process: 13/07375-0 - CeMEAI - Center for Mathematical Sciences Applied to Industry
Grantee:Francisco Louzada Neto
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 17/10118-0 - Study and application of electrochemical technology for the analysis and degradation of endocrine interferents: materials, sensors, processes and scientific dissemination
Grantee:Marcos Roberto de Vasconcelos Lanza
Support Opportunities: Research Projects - Thematic Grants