Cytotoxic and antibacterial polyketide-indole hybrids synthesized from indole-3-carbinol by Daldinia eschscholzii

Two skeletally undescribed polyketide-indole hybrids(PIHs), named indolchromins A and B,were generated from indole-3-carbinol(I3 C) in the fungal culture(Daldinia eschscholzii). The indolchromin structures were elucidated mainly by their 1 D and 2 D NMR spectra with the former confirmed by the single-crystal X-ray crystallographic analysis. Each indolchromin alkaloid was chirally separated into four isomers, whose absolute configurations were assigned by comparing the recorded circular dichroism(CD) spectra with the electronic CD(ECD) curves computed for all optional stereoisomers. Furthermore, the indolchromin construction pathways in fungal culture were clarified through enzyme inhibition, precursor feeding experiment, and energy calculation. The cascade reactions,including decarboxylative Claisen condensation catalyzed by 8-amino-7-oxononanoate synthase(AONS),C(sp3)-H activation, double bond migration, and Michael addition, all undergone compatibly during the fungal cultivation. In an MIC range of 1.3–8.6 μmol/L,(2 S,4 R)-and(2 R,4 S)-indolchromin A and(2 R,4 S)-indolchromin B are inhibitory against Clostridium perfringens, Clostridium difficile, Veillonella sp.,Bacteroides fragilis, and Streptococcus pyogenes.(2 R,4 S)-Indolchromin A and(2 S,4 S)-indolchromin B were cytotoxic against the human breast cancer cell line MDA-MB-231 with IC50 values of 27.9 and131.2 nmol/L, respectively, with the former additionally active against another human breast cancer cell line MCF-7(IC_(50)94.4 nmol/L).

Bioactive Alkaloids from Indole-3-carbinol Exposed Culture of Daldinia eschscholzii

Two new and rare bioactive indoles named dalesindoloids A （1） and B （3）, along with 3-（1H-indole-3ylmethyl）-2-oxindole （2）, were characterized from the indole-3-carbinot （13C）-exposed culture of Daldinia eschscholzii. The absolute configuration of 2 was determined by quantum chemical calculations of the electronic circular dichroism （ECD） spectrum. Dalesindoloids A and B were cytotoxic against the leukemia HL-60 cell line with the IC50 values of 1.0 and 7.4 μmol/L, respectively, with the former being inhibitory on Staphylococcus aureus （MIC： 9.1 μmol/L）. The simultaneous characterization of the alkaloids from the 13C-exposed fungal culture highlighted that the 2,3-epoxyindoline motif can be transformed into both lactam and indolin-3-one moieties. This is the first-time description of the 2,3-epoxyindoline chemical versatility and Wagner-Meerwein rearrangement （WMR） reaction in the microbial culture.

Dalestones A and B, two anti-inflammatory cyclopentenones from Daldinia eschscholzii with an edited strong promoter for the global regulator LaeA-like gene

Replacement of the native promoter of the global regulator Lae A-like gene of Daldinia eschscholzii by a strong gpdA promoter led to the generation of two novel cyclopentenone metabolites, named dalestones A and B, whose structures were assigned by a combination of spectroscopic analysis, modified Mosher's reaction, and electronic circular dichroism(ECD). Dalestones A and B inhibit the gene expression of TNF-α and IL-6 in LPS-induced RAW264.7 macrophages.