Precursor-Directed Production of Bis- and Monopyrrole Phenyl Derivatives by Myrothecium verrucaria and Their Cytotoxic Activity

Abstract

Feeding m-phenylenediamine to Myrothecium verrucaria HPU-ZMN produced eight new phenylpyrrole derivatives, myrodiamines A−H (1−8). Compounds 2 and 5 were likely purification artifacts. In contrast to the monofunctional aniline precursors used previously, the bifunctional diamine is processed along two routes: both amino groups engage in pyrrole formation to give dipyrrole dimers 1−5 or one is cyclized while the other is acylated, affording monopyrrole amides 6−8. Structures were elucidated by 1D/2D NMR and HRESIMS. Compound 3 showed potent cytotoxicity against K562 cells (IC50 = 0.073 μM) and promising activity against NCI-H446, NCI-H446/EP, and MDA-MB-231 cells (IC50 = 0.26−0.51 μM).