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Rapid tools to gain insights into the interaction dynamics of new 8‐hydroxyquinolines with few fungal lines
Author(s) -
Joaquim Angélica Rocha,
Pippi Bruna,
de Cesare Maycon Antonio,
Rocha Débora Assumpção,
Boff Roberta Taufer,
Staudt Keli Jaqueline,
Ruaro Thaís Carine,
Zimmer Aline Rigon,
de Araújo Bibiana Verlindo,
Silveira Gustavo Pozza,
Martins Andreza Francisco,
Teixeira Mario Lettieri,
dos Santos Francisco Paulo,
Fuentefria Alexandre Meneghello,
de Andrade Saulo Fernandes
Publication year - 2019
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13435
Subject(s) - antimicrobial , toxicity , broth microdilution , minimum inhibitory concentration , chemistry , ec50 , antifungal , staphylococcus aureus , sulfonamide , quantitative structure–activity relationship , combinatorial chemistry , in vitro , biochemistry , microbiology and biotechnology , stereochemistry , biology , bacteria , organic chemistry , genetics
The combination of tools such as time‐kill assay with subsequent application of mathematical modeling can clarify the potential of new antimicrobial compounds, since minimal inhibitory concentration ( MIC ) value does not provide a very detailed characterization of antimicrobial activity. Recently, our group has reported that the 8‐hydroxy‐5‐quinolinesulfonic acid presents relevant antifungal activity. However, its intrinsic acidity could lead to an ionization process, decreasing fungal cell permeability. To overcome this potential problem and enhance activity, the purpose of this study was to synthesize and evaluate a novel series of hybrids between the 8‐hydroxyquinoline core and sulfonamide and to prove their potential using broth microdilution method, obtaining the pharmacodynamic parameters of the most active derivatives combining time‐kill studies and mathematical modeling and evaluating their toxicity. Compound 5a was the most potent, being active against all the fungal species tested, with low toxicity in normal cells. 5a and 5b have presented important antibacterial activity against Staphylococcus aureus strain. The EC 50 values obtained by combination of time‐kill studies with mathematical model were similar to those of MIC , which confirms the potential of compounds. In addition, these derivatives are non‐irritant molecules with the absence of topical toxicity. Finally, 5a and 5b are promising candidates for treatment of dermatomycosis and candidiasis.