Drug design of new 5-HT6 antagonists: a QSAR study of arylsulfonamide derivatives

Autor(es)

da Silva, Aldineia P. ^[1] ; de Angelo, Rafaela M. ^[2] ; de Paula, Heberth ^[3] ; Honorio, Kathia M. ^[2] ; da Silva, Alberico B. F. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sao Carlos Inst Chem, Ave Trabalhador Sao Carlense 400, BR-13560970 Sao Carlos, SP - Brazil

^[2] Univ Sao Paulo, Sch Arts Sci & Humanities EACH, BR-03828000 Sao Paulo - Brazil

^[3] Fed Univ Espirito Santo CCENS, Ctr Exact Nat & Hlth Sci, Dept Pharm & Nutr, Campus Alegre, BR-29500000 Alegre - Brazil

• Tipo de documento: Artigo Científico
• Fonte: STRUCTURAL CHEMISTRY; v. 31, n. 4 MAR 2020.
• Citações Web of Science: 0

Resumo

Several studies underscore that the 5-hydroxytryptamine subtype 6 (5-HT6) receptor is intrinsically related to the onset of Alzheimer's disease and its blocking significantly improve the learning and memory processes. In this manuscript, we apply quantitative structure-activity relationship (QSAR) techniques to a series of potential arylsulfonamide-derived 5-HT6 receptor antagonists aiming to design new anti-AD ligands. In order to describe physicochemical properties of the compounds, a plethora of descriptor types was calculated, and then selected by statistical techniques to build models that relate the chemical structure to antagonist activity of these studied ligands. Thereafter, structural variations were performed on the C15, C25, and C47 compounds by analyzing the steric and electrostatic fields as well as 2D maps. At last, the new compounds were submitted to the constructed QSAR models which presented promising results. It is noteworthy that the C4704 compound exhibited the highest biological activity value, surpassing even the values of the compounds used in the construction of the model. In conclusion, the robustness of the model allowed to confidently predict the biological activity values of the designed compounds. (AU)

• Processo FAPESP: 18/06680-7 - Aplicação de ontologias em estudos de química medicinal computacional e relações entre estrutura química e atividade biológica
• Beneficiário: Rafaela Molina de Angelo
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 13/07375-0 - CeMEAI - Centro de Ciências Matemáticas Aplicadas à Indústria
• Beneficiário: Francisco Louzada Neto
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs