MEDICINAL CHEMISTRY | RESEARCH ARTICLE Small-molecule inhibitors of the tuberculosis target, phenylalanyl-tRNA synthetase from Penicillium griseofulvum CPCC-400528

1 * Abstract: Phenylalanyl-tRNA synthetase (PheRS), a member of aminoacyl-tRNA syn- thetase family, was the new target of anti-tubercular drug discovery. In an attempt to fully exploit the new potential anti-tuberculosis drugs presented in micro-organ- isms, we developed a high-throughput screening assay against Mycobacterium tu- berculosis (Mtb) PheRS and then screened a library consisting of 32,000 strains and 1500 natural product-derived compounds. One potent hit extract of Penicillium gris- eofulvum CPCC-400528 was identified. In this study, isopatulin (1), (+)-epiepoformin (2) and gentisyl alcohol (3), three patulin-producing intermediates, together with three indole-tetramic acids, α-cyclopiazonic acid (4), β-cyclopiazonic acid (5) and iso-α-cyclopiazonic acid (6), were isolated and identified as bioactive constituents from P. griseofulvum CPCC-400528. Their structures were elucidated on the basis of spectroscopic data. Compounds 1, 3, 4, and 5 exhibited Mtb PheRS-inhibiting activi- ties, as well as moderate to weak anti-tuberculosis activities against Mtb H37Rv.