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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.)

Diaminomaleonitrile derivatives as new potential antichagasic compounds: a study of structure-activity relationships

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Author(s):
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de Oliveira, Aldo S. [1, 2] ; Mello, Lucas dos S. [3] ; Ogihara, Camila H. [4] ; Doring, Thiago H. [1] ; Palomino-Salcedo, David L. [2] ; Michelan-Duarte, Simone [2] ; Ferreira, Leonardo L. G. [2] ; Souza, Julia M. [2] ; Davila-Rodriguez, Maria Jose [2] ; da Cruz Junior, Jose W. [1] ; Dockal, Edward R. [3] ; Andricopulo, Adriano D. [2]
Total Authors: 12
Affiliation:
[1] Univ Fed Santa Catarina, Dept Exact Sci & Educ, Campus Blumenau, Rua Joao Pessoa 2750, BR-89036256 Blumenau - Brazil
[2] Univ Sao Paulo, Ctr Res & Innovat Biodivers & Drug Discovery, Inst Phys Sao Carlos, Lab Med & Computat Chem, Av Joao Dagnone 1100, BR-13563120 Sao Carlos, SP - Brazil
[3] Fed Univ Sao Carlos UFSCar, Dept Chem, Lab Inorgan Synth Catalysis & Kinet, Rodovia Washington Luis S-N Km 235, Sao Carlos, SP - Brazil
[4] Univ Campinas UNICAMP, Chem Inst, R Josue de Castro 126, Cidade Univ, Campinas, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Source: Future Medicinal Chemistry; v. 13, n. 24 OCT 2021.
Web of Science Citations: 0
Abstract

Background: Schiff bases are synthetically accessible compounds that have been used in medicinal chemistry. Methods \& results: In this work, 27 Schiff bases derived from diaminomaleonitrile were synthesized in high yields (80-98%). Molecular docking studies suggested that the Schiff bases interact with the catalytic site of cruzain. The most active cruzain inhibitor, analog 13 (IC50 = 263 nM), was predicted to form an additional hydrophobic contact with Met68 in the binding site of the enzyme. A strong correlation between the IC50 values and ChemScore binding energies was observed (R = 0.99). Kernel-based 2D quantitative structure-activity relationship models for the whole dataset yielded sound correlation coefficients (R-2 = 0.844; Q(2) = 0.719). Conclusion: These novel and potent cruzain inhibitors are worthwhile starting points in further Chagas disease drug discovery programs. (AU)

FAPESP's process: 15/06392-3 - Cu(II)/Co(III), Cu(II)/Fe(III) and Cu(II)/Ni(II) bimetallic complexes containing Schiff bases: potential catalyzers on the oxidation of catechols
Grantee:Edward Ralph Dockal
Support Opportunities: Regular Research Grants
FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
Grantee:Glaucius Oliva
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC