Synthesis, in silico Study, Theoretical Stereochemistry Elucidation and Antifungal Activity of New Imides Derived from Safrole

• Autor(a) principal: Vilela,Raquel F.
• Data de Publicação: 2020
• Outros Autores: Costa,Normando A. S., Souza,Helivaldo D. S., Cruz,Luiz E. G., Assis,Kelyonara M. S. de, Lima,Edeltrudes O., Cordeiro,Laísa V., Lira,Bruno F., Athayde-Filho,Petronio F. de, Rocha,Gerd B., Barbosa-Filho,José M.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Journal of the Brazilian Chemical Society (Online)
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532020001002091
• topic: imides; safrole; Candida; Cryptococcus

Ten imides derived from safrole, 4a-4j, were synthesized and their structures were fully characterized by infrared (IR) spectroscopy, 1H and 13C nuclear magnetic resonance (NMR) spectroscopy and high resolution mass spectrometry (HRMS) analysis. Among the ten imides studied, eight are new. The compounds were evaluated in an in silico study and showed strong to moderate antifungal activity against various strains of Candida and Cryptococcus. In particular, compounds 4b, 4c and 4h exhibited strong antifungal activity, with minimum inhibitory concentration (MICs) between 0.17-0.73 µmol mL-1. The compound 4j exhibited antifungal activity with MIC 1.28 µmol mL-1 for all strains tested. In silico studies of the parameters of Lipinski’s rule of five indicated that these compounds are potential new drug candidates. The predict oral bioavailability can be evaluated through these parameters. In addition, a computational study helped assigning the stereochemistry of compound 4j, where the synthesized mixture is composed by two stereoisomers, 4j(1) (SRR) and 4j(2) (RSS).