New Guaiane-Type Sesquiterpenoids Biscogniauxiaols A–G with Anti-Fungal and Anti-Inflammatory Activities from the Endophytic Fungus Biscogniauxia Petrensis

Abstract

Seven undescribed guaiane-type sesquiterpenoids named biscogniauxiaols A–G (1–7) were isolated from the endophytic fungus Biscogniauxia petrensis on Dendrobium orchids. Their structures were determined by extensive spectroscopic analyses, electronic circular dichroism (EC) and specific rotation (SR) calculations. Compound 1 represented a new family of guaiane-type sesquiterpenoids featuring an unprecedented [5/6/6/7] tetracyclic system. A plausible biosynthetic pathway for compounds 1–7 was proposed. The anti-fungal, anti-inflammatory and multidrug resistance reversal activities of the isolates were evaluated. Compounds 1, 2 and 7 exhibited potent inhibitory activities against Candida albicans with MIC values ranging from 1.60 to 6.30 μM, and suppressed nitric oxide (NO) production with IC50 ranging from 4.60 to 20.00 μM. Additionally, all compounds (100 μg/mL) enhanced the cytotoxicity of cisplatin in cisplatin-resistant non-small cell lung cancer cells (A549/DDP). This study opened up a new source for obtaining bioactive guaiane-type sesquiterpenoids and compounds 1, 2, and 7 were promising for further optimization as multifunctional inhibitors for anti-fungal (C. albicans) and anti-inflammatory purposes.

Phytochemistry and Pharmacology of Sesquiterpenoids from Atractylodes DC. Genus Rhizomes

“…Farnesyl pyrophosphate (FPP) has been recognized as a sesquiterpenoid biosynthetic precursor and generates diverse sesquiterpene carbon skeletons via irregular coupling reactions [ 75 , 76 ]. FPP undergoes one cyclization or more to form germacryl cations, which lose a proton to produce the intermediate germacrenes A/B, followed by a series of protonation, structural rearrangements, and substitutions of various hydroxyls via oxidation reactions to produce eudesmane, guaiane, spirovetivane, isopterocarpolone, and eremophilane skeletons [ 77 , 78 , 79 ]. The possible biosynthetic pathways of various sesquiterpene types are shown in Figure 1 .…”

Secondary Metabolites of Biscogniauxia: Distribution, Chemical Diversity, Bioactivity, and Implications of the Occurrence

“…They are the most diverse group of terpenoids [ 63 ]. Seven new sesquiterpenoids of the guanine type, namely biscogniauxiaol A–G ( 90 – 96 ), were successfully isolated from the endophytic fungus Biscogniauxia petrensis MFLUCC 14-0151 on Dendrobium orchids [ 23 ]. The isolated biscogniauxiaol A–G ( 90 – 96 ) ( Figure 21 ) is a colorless solid that was then tested for its biological activity for antifungal, anti-inflammatory, and anti-cancer activities, which will be explained further in Section 2 .…”

“…Among these, an endophytic fungal strain belonging to Biscogniauxia has been identified and reported to produce compounds that are effective in anticancer tests. Some of these compounds include cerebroside A ( 3 ), cerebroside C ( 4 ), 7-hydroxy-5-methoxy-4,6-dimethylphthalide ( 54 ), and 6-[(1 R )-1-hydroxy-1-methyl-2-propenyl]-4-methoxy-3-methyl-2 H -pyran-2-one ( 56 ), nectriapyrone ( 59 ) [ 11 ], biscogniacid A ( 82 ), biscognienyne A-E ( 83 – 86 ), dimericbiscognienynes A–C ( 87 – 89 ) [ 21 , 22 ], biscogniauxiaol A–F ( 90 – 95 ) [ 23 ], pogostol ( 103 ), xylariterpenoids A–B ( 107 , 108 ), xylariterpenoids L–N ( 109 – 111 ), (1 R ,2 S ,6 R ,7 S )-1,2-dihydroxy-α-bisabolol ( 112 ) [ 11 ]. Subsequently, compounds ( 54 ), ( 103 ), ( 105 ), and ( 109 ) showed significant toxicity against HeLa cells with an IC 50 range between 8.64 ± 1.22 and 31.16 ± 4.12 μg/mL [ 11 ].…”

“…Subsequently, compounds ( 54 ), ( 103 ), ( 105 ), and ( 109 ) showed significant toxicity against HeLa cells with an IC 50 range between 8.64 ± 1.22 and 31.16 ± 4.12 μg/mL [ 11 ]. Meanwhile, compounds 90 – 95 showed weak reversal activity against cisplatin-resistant A549/DDP cells [ 23 ].…”

“…Biscogniauxia rosacearum, first recognized as a pathogen causing grape stem disease in Paveh vineyards (western Iran), produces meso-2,3butanediol (115). (3R)-5-methylmellein (22), (3R)-5-methyl-6-methoxymellein (23), tyrosol (47). In addition, nectriapyrone (59) was produced as a phytotoxin from the same fungal strain isolated from oak trees in the Zagros forest in Gilan-e Gharb, Kermanshah Province.…”