COX-2 and iNOS inhibitory epimeric meroterpenoids from Ganoderma cochlear and structure revision of cochlearol Q

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

“…43 F I G U R E 2 (Continued) (±)-Chizhines A and B (45)(46)(47)(48) and ganadone D (49) comprising a five-membered lactone ring formed by the carboxyl group and the tail isoprene unit, were respectively described in the investigation of G. lucidum and G. cochlear, their absolute configurations were assigned by ECD calculations. 30,37 Chizhine B was also identified from G. sinensis. 49 Investigation of G. applanatum led to the isolation of a class of GMs with a furan ring formed in the chain, (±)applanatumols P, Q and R (50-55).…”

“…24,45 In addition, (±)-cochlearol Q (348 and 349), ganadones A-C (350, 351 and 355), 3',10'-di-epi-ganadone A (352), 10'-epi-ganadones A and B (353 and 354), and 3'-epi-ganadone A (356) featuring an adjacent 6',7'-bifuran ring system, were characterized from G. cochlear. 30,72 Of which, the planar structures of racemates (±)-cochlearol Q (348 and 349) were recently revised by Sura et al; ganadone B (351) and 10'-epi-ganadone B (354) were discovered to have inhibitory effects against iNOS and COX-2. 30 The absolute stereochemistries of (±)-cochlearol E (342 and 343), (±)-ganotheaecolumol E (346 and 347), ganadones A-C (350, 351 and 355), 3',10'-di-epi-ganadone A (352), 10'-epi-ganadones A and B (353 and 354), and 3'-epi-ganadone A (356) were elucidated by computational methods and X-ray analysis.…”

“…30,72 Of which, the planar structures of racemates (±)-cochlearol Q (348 and 349) were recently revised by Sura et al; ganadone B (351) and 10'-epi-ganadone B (354) were discovered to have inhibitory effects against iNOS and COX-2. 30 The absolute stereochemistries of (±)-cochlearol E (342 and 343), (±)-ganotheaecolumol E (346 and 347), ganadones A-C (350, 351 and 355), 3',10'-di-epi-ganadone A (352), 10'-epi-ganadones A and B (353 and 354), and 3'-epi-ganadone A (356) were elucidated by computational methods and X-ray analysis. Of note, each of these compound names, cochlearols E and F, possesses two different GM structures, the four structures were all generated from G. cochlear, and cochlearols E and F (342-345) described here were reported in 2019.…”

“…Ganodercins G-K and M-P (365, 366, 357, 358, 371, 369, 362, 367, and 374), 3-epi-ganodercins K and P (372 and 375), (±)-cochlearol H (359 and 360), cochlearol G (364), ganadone E (377), gancochlearols G and H (384 and 385) were generated from G. cochlear, and the structure of cochlearol G (364) was revised by Qin et al in a recent study. 24,28,30,33,46 In an investigation of G. theaecolum, ganotheaecoloids A, B, D-F, and J (389, 390, 363, 373, 361, and 386), ganoresinain C (376), and racemates (±)-ganotheaecoloids C and G-I (368, 370, and 378-383) were characterized; (+)-ganotheaecoloid G (378) and (−)-ganotheaecoloid H (381) are epimers. 54 Of which, ganotheaecoloids C, D, and G, and (±)ganotheaecoloid J (386 and 387) were also obtained from G. australe; ganotheaecoloid F (361) was also found from G. cochlear; ganoresinain C (376) and ganoresinoid E (388) were first identified from G. resinaceum.…”

“…28,30 Biological activities including the inhibitory effects of ganodercin M (369) against the expression of extracellular matrix components, the significant suppressive activity of ganodercin I (357), 3-epi-ganodercin K (372), and ganotheaecoloid F (361) towards the migration of BT549 cells, the upregulation effect of ganodercins L, M and K (368, 369 and 371) and 3-epi-ganodercin P (375) on the expression of p-AMPK, and the dose-dependent suppressive effect of ganadone E (377) on iNOS and COX-2, were proposed recently. 28,30 Besides, gancochlearols G and H (384 and 385), and ganotheaecoloid J (386 and 387) exerted potent inhibitory effect towards COX-2; ganoresinoid E (388) inhibits NO in LPS-induced BV-2 microglia cells; and ganotheaecoloid G demonstrated potent neuroprotective effect in glutamate-stimulated SH-SY5Y cells. 46,52,54,88 GMs comprising a terminal 6/6 fused ring motif are presented by cochlearols N-P (391, 392, and 394) from G. cochlear, ganoresinain D (393) from G. resinaceum, and baoslingzhine A (395) from G. lucidum.…”