Antifungal activity of tri- and tetra-thioureido amino derivatives against different Candida species.
The in vitro antifungal activity of six thioureido substituted amines (P1-P6) was evaluated against Candida species, including Candida albicans, C. glabrata, C. krusei and C. parapsilosis. These tri- and tetra-thioureido amino derivatives with different methylation levels were synthesised through easy synthetic routes to evaluate their antifungal properties against Candida species. Among all studied derivatives, the tri-(2-thioureido-ethyl)-amine (P1) was the most active compound inhibiting C. albicans and C. glabrata at a concentration of 0.49 μg ml(-1); P3, the N,N',N'',N'''-hexamethyl-derivative, also showed inhibitory activity against C. albicans and C. glabrata, but in higher concentrations (250 μg ml(-1) ). The N,N',N'',N'''-tetramethylated amine (P5) only inhibited the growth of C. glabrata, but its corresponding N,N',N'',N'''-octamethyl derivative (P6) was also active against C. glabrata (125 μg ml(-1)) and it was the only compound active against C. parapsilosis. P2 and P4 showed no significant antifungal activity. The structure-activity relationship of the thioureido-substituted derivatives indicates that the molecular branching and the alkylation levels can influence the antifungal activity. This study demonstrated that thioureido derivatives exhibited significant antifungal activity against Candida species and that they can be considered as a very promising bioactive lead compound to develop novel antifungal agents.
Oliveira
S R
SR
Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Nogueira
L J
LJ
Donnici
C L
CL
Magalhães
T F F
TF
Martins
C V B
CV
Montanari
C A
CA
Resende
M A
MA
D000588:Amines / Q000737:chemistry* / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects*; D006801:Humans; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000588:Amines; D000935:Antifungal Agents; D013890:Thiourea