From an actinomycete strain,
Streptomyces sp. K99-5041, lanopylins A
1, B
1, A
2 and B
2 were isolated as new natural products that inhibited the reaction of recombinant human lanosterol synthase. The crude extract from the whole broth of this strain was fractionated by silica gel column chromatography to afford an active fraction that showed a single spot on TLC. Detailed analyses of this fraction with liquid chromatography-atmospheric pressure chemical ionization mass spectrometry revealed that it contained 20 homologous compounds with differing side chain lengths. The fraction was separated by preparative HPLC to afford four of these homologues, lanopylins A
1, B
1, A
2 and B
2. Detailed spectroscopic analyses of these isolated compounds led to the identification of their structures. Lanopylins A
1 and B
1 were (3
E)-isohexadecylmethylidene-2-methyl-1-pyrroline and (3
E)-hexadecylmethylidene-2-methyl-1-pyrroline, respectively, and lanopylins A
2 and B
2 were homologues with the insertion of one
cis-ethylenylidene in the side chain of lanopylins A
1 and B
1, respectively. These compounds inhibited recombinant human lanosterol synthase with IC
50 values of 15, 18, 33, and 41μM, respectively.
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