Bioactive Alkaloids from Indole‐3‐carbinol Exposed Culture of Daldiniaeschscholzii

Abstract

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‐carbinol (I3C)‐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 I3C‐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.

Dalmanol biosyntheses require coupling of two separate polyketide gene clusters

“…This rationalization agrees with the oxygenation pattern of 1 and 2 and the monooxygenase-catalyzed 2,3-epoxidation of some indole motifs (a mimic of the polarized double bond of 4 , Fig. 3) in the fungal culture 46. The inter-cluster coupling gains reinforcements from the production of 1 and 2 via the heterologous co-expression of pksTL, ChrA and ChrB in A. oryzae , and through the co-culture of the two (co-)transformants, pksTL -AO and ChrA / ChrB -AO.…”

Recent progress in biodiversity research on the Xylariales and their secondary metabolism

“…Miscellaneous secondary metabolites from Hypoxylaceae (Fig. 14) From a mantis gut-derived D. eschscholtzii that also produced the dalescones, cultures supplemented with indole-3-carbinol yielded two (bis-)indole natural products named dalesindoloids A (81) to B [111]. Assessment of their cytotoxicity showed that 81 was strongly active against HL-60 cells (IC 50 1.0 µM), while being less active against several other cell lines.…”

<p class="Author"> <p class="Title" style="text-indent:0mm;"> Natural Products from the genus <i>Daldinia</i> and Their Bioactivities

“…Li et al From the indole-3-carbinol exposed culture of D.eschscholzii, Lin et al [13] obtained two new alkaloids named dalesindoloids A (31) and B (32), shown in Figure 3. And then, this group [14] found two skeletally undescribed polyketide-indole hybrids from the indole-3-carbinol-exposed culture of D. eschscholzii named indolchromins A and B (33-34).…”

“…[11] Dalesindoloid A (31) displayed moderate inhibition on the growth of S. aureus with its MIC value disclosed to be 9.1 μM, the MIC value of co-assayed streptomycin, 0.5 μM. [13] Daldispones B (56) showed moderate antimicrobial activity against Staphylococcus aureus, Enterococcus faecalis and Bacillus cereus with MIC of 32, 16, 32 μg/mL, respectively. [22] Helicascolide C (13), compound ( 15) and 8-hydroxylhelicascolide A (38), 6,8-dihydroxy-3-methyl-3,4dihydroisocoumarin (40) and compound (57) also showed mild antibacterial activity.…”

“…[14] Dalesindoloid A (31) displayed selective cytotoxicity against the HL-60 cell line with an IC50 value of 1.01 μM, and dalesindoloid B (32) showed discernible cytotoxicity against six of the seven cancer cell lines with an IC50 range of 7.44-14.64 μM. [13] 6,8-Dihydroxy-3-methyl-3,4-dihydroisocoumarin (40), (22R)hydroxylanosta-7,9(11),24-trien-3-one (41) and ergosterol (42) showed moderate cytotoxicity against four cancer cells, KB (a human epidermal carcinoma), MCF7 (human breast carcinoma), SK-LU-1 (human lung carcinoma) and HepG2 (hepatocellular carcinoma). [18] Compounds (2, 6, and 7) showed cytotoxic with IC50 values of 0.22, 14.34, and 10.04 μg/mL.…”