RESUMO
Zingerone (1) and both chiral forms of zingerol (2) were obtained from dehydrozingerone (3) by biotransformation with filamentous fungi. The bioconversion of 3 with A. fumigatus, G. candidum or R. oryzae allowed the production of 1 as the sole product at 8 h and in 81%-90% at 72 h. In turn, A. flavus, A. niger, C. echinulata, M. circinelloides and P. citrinum produced 1 at 8 h, but at 72 h alcohol 2 was obtained as the major product (74%-99%). Among them, A. niger and M. circinelloides led to the anti-Prelog zingerol (R)-2 in only one step with high conversion rates and ee. Instead, C. echinulata and P. citrinum allowed to obtain (S)-2 in only one step, with high conversion rates and ee. Both chiral forms of 2 were tested for antifungal properties against a panel of clinically important fungi, showing that (R)-, but not (S)-2 possessed antifungal activity.
Assuntos
Antifúngicos/farmacologia , Biocatálise/efeitos dos fármacos , Aromatizantes/metabolismo , Fungos/metabolismo , Guaiacol/análogos & derivados , Biotransformação/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Ésteres/química , Aromatizantes/química , Aromatizantes/farmacologia , Fungos/efeitos dos fármacos , Guaiacol/química , Guaiacol/metabolismo , Guaiacol/farmacologia , Testes de Sensibilidade Microbiana , Espectroscopia de Prótons por Ressonância Magnética , Estereoisomerismo , Fatores de TempoRESUMO
The natural product zanthosimuline and its 18 analogues were easily prepared from simple starting materials and evaluated in vitro against postharvest fruit fungal pathogens. The panel included Penicillium digitatum, Botrytis cinerea, Monilinia fructicola, and Rhizopus stolonifer; all of them causing relevant economic losses worldwide. The minimum inhibitory concentrations and minimum fungicidal concentrations of each compound were determined, and the main structure-activity relationships were established. The biological activity observed was strongly increased by maintaining the prenyl side chain of zanthosimuline in an N-demethylated derivative. In addition, the compound that is the most active in the in vitro evaluation was tested in freshly harvested peaches exhibiting a promising brown rot control profile, comparable to the commercial agent carbendazim but demonstrating less toxicity against human liver cell lines.
RESUMO
The antifungal activity of a library of twenty-four aromatic methoximes was examined against five representative postharvest phytopathogenic fungi. The panel included Penicillium digitatum, Penicillium italicum, Rhizopus stolonifer, Botrytis cinerea and Monilinia fructicola, all of which cause relevant economic losses worldwide as a result of affecting harvested fruits. The minimum inhibitory concentrations and minimum fungicidal concentrations of each compound were defined and the main structure-activity relationships were determined. Although other congeners were more potent, drug likeliness considerations pointed to the methoxime derived from 2,4-dihydroxypropiophenone as the compound with the most suitable profile. The morphology of the colonies of the fungal strains treated with the methoxime was examined microscopically and the compound was also tested in freshly harvested peaches and oranges, exhibiting promising control profiles in both fruits, similar to those of the commercial agents Imazalil and Carbendazim.
Assuntos
Antifúngicos/química , Antifúngicos/farmacologia , Frutas/microbiologia , Oximas/química , Ascomicetos/efeitos dos fármacos , Botrytis/efeitos dos fármacos , Citrus sinensis/efeitos dos fármacos , Citrus sinensis/microbiologia , Frutas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Oximas/farmacologia , Penicillium/efeitos dos fármacos , Prunus persica/efeitos dos fármacos , Prunus persica/microbiologia , Rhizopus/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
The antifungal activity of pterophyllin 2, pterophyllin 4, a 5-desmethyl analog of the latter and some of their synthetic intermediates, against three postharvest phytopathogenic fungi, was evaluated. The target fungi were Rhizopus stolonifer, Botrytis cinerea and Monilinia fructicola, which affect fruits worldwide, causing important economic losses. The tests were carried out with imazalil and carbendazim as positive controls. Minimum inhibitory concentrations and minimum fungicidal concentrations were determined, and the morphology of the colonies was examined microscopically. In liquid medium, it was found that pterophyllin 4 exhibited selective fungicidal activity toward M. fructicola, whereas its congener pterophyllin 2 proved to be less potent and not selective and the 5-desmethyl analog of pterophyllin 4 displayed a different activity profile. Morphological changes were observed in the colonies exposed to pterophyllin 4. The results highlighted the importance of small structural features for the antifungal behavior and also suggested that, in Nature, the pterophyllins may act as plant defenses against pathogens.