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7209382 
Journal Article 
alpha-Bisabolol inhibits Aspergillus fumigatus Af239 growth via affecting microsomal Delta(24) -sterol methyltransferase as a crucial enzyme in ergosterol biosynthesis pathway 
Jahanshiri, Z; Shams-Ghahfarokhi, M; Asghari-Paskiabi, F; Saghiri, R; Razzaghi-Abyaneh, M; , 
2017 
1 
World Journal of Microbiology and Biotechnology
ISSN: 0959-3993
EISSN: 1573-0972 
SPRINGER 
DORDRECHT 
33 
3 
55 
English 
28224386 
WOS:000398100300014 
Finding new compounds with antifungal properties is an important task due to the side effects of common antifungal drugs and emerging antifungal resistance in fungal strains.Delta(24) -sterol methyltransferase (24-SMT) is a crucial enzyme that plays important roles in fungal ergosterol biosynthesis pathway and is not found in humans. In the present study, the effects of alpha-bisabolol on Aspergillus fumigatus Af239 growth and ergosterol synthesis on the base of 24-SMT enzyme activity were studied; in addition, the expression of erg6, the gene encoded 24-SMT, was considered. To our knowledge, this is the first report demonstrating that alpha-bisabolol inhibits A. fumigatus growth specifically via suppressing fungal 24-SMT. Since this enzyme is a specific fungal enzyme not reported to exist in mammalian cells, alpha-bisabolol may serve as a lead compound in the development of new antifungal drugs. Fungi were cultured in presence of serial concentrations of alpha-bisabolol (0.281-9 mM) for 3 days at 35 degrees C. Mycelia dry weight was determined as an index of fungal growth and ergosterol content was assessed. Microsomal 24-SMT activity was assayed in presence of alpha-bisabolol as an inhibitor, lanosterol as a substrate and [methyl-H-3] AdoMet (S-Adenosyl methionin). In addition, the expression of erg 6 gene (24-SMT encoding gene) was determined after treatments with various concentrations of alpha-bisabolol. Our results demonstrated that a-bisabolol strongly inhibited A. fumigatus growth (35.53-77.17%) and ergosterol synthesis (26.31-73.77%) dose-dependently and suppressed the expression of erg 6 gene by 76.14% at the highest concentration of 9 mM. alpha-bisabolol inhibited the activity of 24-SMT by 99% at the concentration of 5 mM. Taken together, these results provides an evidence for the first time that alpha-bisabolol inhibits A. fumigatus Af239 growth via affecting microsomal Delta(24) -sterol methyltransferase as a crucial enzyme in ergosterol biosynthetic pathway.