Meroterpenoid Dimers from Ganoderma Mushrooms and Their Biological Activities Against Triple Negative Breast Cancer Cells

Abstract

(±)-Dimercochlearlactones A−J (1–10), ten pairs of novel meroterpenoid dimers and one known spirocochlealactone A (11), were isolated from Ganoderma mushrooms. The structural elucidation of new compounds, including their absolute configurations, depends on spectroscopic analysis and electronic circular dichroism (ECD) calculations. Biological studies showed that (+)- and (–)-2, (–)-3, and (+)- and (–)-11 are cytotoxic toward human triple negative breast cancer (TNBC) cells (MDA-MB-231) with IC50 values of 28.18, 25.65, 11.16, 8.18, and 13.02 μM, respectively. Wound healing assay revealed that five pairs of meroterpenoids (±)-5−(±)-8 and (±)-10 could significantly inhibit cell mobility at 20 μM in MDA-MB-231 cells. The results provide a new insight into the biological role of Ganoderma meroterpenoids in TNBC.

Insights into Ganoderma fungi meroterpenoids opening a new era of racemic natural products in mushrooms

“…Of which, (±)ganodilactone (532 and 533) and (±)-spirocochlealactone A (540 and 541) were also found from G. leucocontextum and G. lucidum, respectively. 85,99 Interestingly, meroterpenoid dimers which possess stereogenic centers generated from G. cochlear were all obtained as racemic.…”

“…Another pair of enantiomers named (+)-and (−)-dimercochlearlactone D (522 and 523) were elucidated absolute configurations by employing ECD calculations. 99 Enantiomers of (±)-dispirocochlearoid A (526 and 527) comprise an unusual 6/6/5/6/6/6 ring backbone; they were discovered to have selective inhibition on COX-2. 8 Their absolute configurations were assigned by using ECD calculations.…”

Structural diversity, hypothetical biosynthesis, chemical synthesis, and biological activity ofGanodermameroterpenoids

“…The benzodihydrofuranone fragment of (−)-dimercochlearlactone F ( 127 ) 73 was speculated to be constructed through a nucleophilic addition of C-5a of ganomycin F ( 18 ) 21 to C-14′ of cochlearin I ( 21 ), 31 and a Michael addition from 4a-OH to the α,β-unsaturated ketone (C-1′/C-2′/C-3′) (Fig. 32).…”

“…For a plausible biosynthetic pathway of (−)-dimercochlearlactone H ( 128 ), 73 ganomycin F ( 18 ) and ganodercin A ( 10 ) are regarded as two precursors. In the first step, C-2 of ganomycin F ( 18 ) could attack the ketone at C-1a′ of ganodercin A ( 10 ), while 1a′-OH could esterify with 14a′-COOH to generate a γ-lactone.…”

“…(+)-Dimercochlearlactone B ( 129 ) from G. cochlear 73 has the same dihydrofuranone ring as that of 127 , but its unique 1,2,4-trisubstituted phenylethylene connecting with 5,9-trimethy-4,8-dien-dodecanoic acid suggests that 129 could have different biosynthetic pathway. First, fornicin C ( 24 ) could be converted into two precursors A and B via a redox reaction.…”