Two New Classes of T-Type Calcium Channel Inhibitors with New Chemical Scaffolds from Ganoderma cochlear

Abstract

T-type calcium channel (TTCC) inhibitors hold great potential for the treatment of a variety of neurological disorders. Cochlearoids A–E (1–5), five pairs of dimeric meroterpenoid enantiomers, and cochlearines A (6) and B (7), two pairs of enantiomeric hybrid metabolites, were isolated and characterized from Ganoderma cochlear. Biological evaluation found that compounds (+)-1, (−)-3, and (±)-6 significantly inhibited Cav3.1 TTCC and showed noticeable selectivity against Cav1.2, Cav2.1, Cav2.2, and Kv11.1 (hERG) channels.

Meroterpenoids from Ganoderma Species: A Review of Last Five Years

“…In TGF- β 1-induced human renal proximal tubular cells, applanatumin A ( 123 ) diclosed potent antifibrotic activity [ 17 ]. Cochlearoids A–E ( 124 – 128 ) containing a unique methanobenzo[ c ]oxocino[2,3,4- ij ]-isochromene scafflod were also constructed by two meroterpenoids [ 49 ]. Among them, (+)- 124 , and (−)- 126 significantly inhibited Cav3.1 TTCC and showed noticeable selectivity against Cav1.2, Cav2.1, Cav2.2 and Kv11.1 (hERG) channels [ 49 ].…”

“…Cochlearoids A–E ( 124 – 128 ) containing a unique methanobenzo[ c ]oxocino[2,3,4- ij ]-isochromene scafflod were also constructed by two meroterpenoids [ 49 ]. Among them, (+)- 124 , and (−)- 126 significantly inhibited Cav3.1 TTCC and showed noticeable selectivity against Cav1.2, Cav2.1, Cav2.2 and Kv11.1 (hERG) channels [ 49 ]. The combination of two chian-contained GMs formed (+)-ganodilactone ( 129 ), cochlearoids F and G ( 130 and 131 ) [ 50 , 51 ].…”

Cytotoxic and N-Acetyltransferase Inhibitory Meroterpenoids from Ganoderma cochlear

“…So far, more than 150 Ganoderma meroterpenoids have been reported from Ganoderma species, of which more than two thirds were characterized by us. These structurally diverse meroterpenoids were disclosed to have anti-fibrotic [ 7 , 8 ], neuroprotective [ 9 ], antiinflammatory, and antioxidant properties [ 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. As a continuation of our research on Ganoderma species, Ganoderma cochlear was investigated which resulted in the isolation of cochlearines A and B, cochlearoids A–K [ 8 , 16 ], cochlearols A and B [ 17 ], and ganocochlearines C–I [ 18 ].…”

Five new compounds from the fungus Ganoderma petchii

“…lucidum [4], since then, several structurally novel and biologically active meroterpenoids were isolated and characterized [5][6][7][8][9][10]. During our continuous research on Ganoderma species, G. petchii was investigated.…”