RESUMO
The synthesis of several monomeric and dimeric steroidal [1,2,4]triazolo[1,5-a]pyrimidines (TPs) derived from steroids are described. These derivatives were prepared from α,ß-unsaturated carbonyl compounds through a Claisen Schmidt condensation and rearrangement of the spiro moiety followed by a cycloaddition with 3-amino-1,2,4-triazole. The antiproliferative activity of compounds 7, 13-15 was tested against human cancer cells; several IG50 values were below 10µM.
Assuntos
Pirimidinas/química , Esteroides/síntese química , Triazóis/química , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Estereoisomerismo , Esteroides/química , Esteroides/farmacologiaRESUMO
Maize is one the most important staple foods in the world. However, numerous pests, such as fungal pathogens, e.g., Fusarium verticillioides, and insects, such as Sitophlilus zeamais, attack maize grains during storage. Many F. verticillioides strains produce fumonisins, one of the most important mycotoxin that causes toxic effects on human and animal health. This situation is aggravated by the insect fungal vector, Sitophlilus zeamais, which contributes to the dispersal of fungal spores, and through feeding damage, provide entry points for fungal infections. The aim of this study was to evaluate in vitro bioassays, the antifungal activity on F. verticillioides M3125 and repellent effects against S. zeamais of ketone terpenes. In addition, we performed Quantitative structure-activity relationship (Q-SAR) studies between physico-chemical properties of ketone terpenes and the antifungal effect. Thymoquinone was the most active compound against F. verticillioides (Minimum Inhibitory Concentration, MIC: 0.87) affecting the lag phase and the growth rate showing a total inhibition of growth at concentration higher than 2 mM (p < 0.05). The Q-SAR model revealed that the antifungal activity of ketone compounds is related to the electronic descriptor, Pi energy. Thymoquinone showed a strong repellent effect (-77.8 ± 8.5, p < 0.001) against S. zeamais. These findings make an important contribution to the search for new compounds to control two stored pests of maize.
RESUMO
An efficient and facile synthesis of fused, substituted and spiro pyrazoline steroid derivatives through a cycloaddition reaction of different α,ß-unsaturated ketones with hydrazine acetate in acetic acid is reported. Depending on the starting material, the ring closure reaction provided a mixture of two steroidal pyrazoline epimers that were separated and studied by NMR techniques. In one case it was possible to isolate and characterize the hydrazone derivative as the reaction intermediate, which confirms the mechanism proposed in the literature [11,25,26].