Bipolaricins A–I, Ophiobolin-Type Tetracyclic Sesterterpenes from a Phytopathogenic Bipolaris sp. Fungus

Abstract

A preliminary phytochemical investigation on the EtOAc extracts of the fungus Bipolaris sp. TJ403-B1 resulted in the identification of 12 ophiobolin-type phytotoxins (1−12), including nine new ones, termed bipolaricins A−I (1−9). The structures of 1−9 were elucidated via spectroscopic data (including HRESIMS and 1D and 2D NMR) and single-crystal X-ray diffraction (Cu Kα) analyses. All of the isolated compounds were tested in terms of HMG-CoA reductase inhibitory, anti-inflammatory, and cytotoxic activities. Compound 10 showed HMG-CoA reductase inhibitory activity (IC 50 = 8.4 ± 0.4 μM), and 2, 3, and 10−12 showed significant inhibitory potency against lipopolysaccharide (LPS)-induced nitric oxide production, with IC 50 values in the range of 5.1 ± 0.3 to 20 ± 1 μM. Further experiments showed that 10 could significantly inhibit the production of IL-1β, RANTES, MIP-1β, and TNF-α as well as enhance the release of IL-13 in macrophages through the inhibition of HO-1 induction as well as the NF-κB pathway. These findings provide a scientific rationale for an anti-inflammatory therapeutic and a template for a new HMG-CoA reductase inhibitor to produce a potential anti-hyperlipidemia agent.

Antioxidant spiropharanone, an undescribed variant of trans ‐decalin spiro‐ γ ‐lactone, from pharaoh cuttlefish Sepia pharaonis : Twin inhibitors of inflammatory 5‐lipoxygenase and serine protease dipeptidyl peptidase‐4

“…Earlier report of literature established the anti-inflammatory activity with effects on NO production in the LPS-induced RAW264.7 cell lines of the compounds with spirocyclic motifs in fusion with a furan ring (An et al, 2016). Oxygenated spiro undecane compounds extracted from the marine macroalga Gracilaria salicornia exhib- the key reasons of promising pharamacological activities including anti-hyperglycemia (Fatahala et al, 2018;Liu et al, 2019).…”

“…Over the past few decades, spiro-based heterocyclic systems gained considerable attention among the scientific community owing to their structural diversity and pharmacological activities (Zheng et al, 2014). Among the spirocyclic frameworks, the natural products with spirolactone moieties were extensively studied for their pharmacological profiling, particularly with regard to antiinflammatory, anti-proliferative, and anti-hyperglycemic activities (Fatahala et al, 2018;Liu et al, 2019). The asymmetric nature of spiro carbon in the spiro-based compounds coupled with superior conformational rigidity and flexible balance along with their structural novelty made them important candidates for pharmacophore discovery (Chupakhin et al, 2019).…”

Spirocyclic Motifs in Natural Products

“…They were tested for HMGCoA reductase inhibition as well as anti-inflammatory and cytotoxic activities. The biological activity discovered provided the basis for considering these compounds as leads for antiinflammation and antihyperglycemic therapy developments [54].…”

The Biosynthesis and Transport of Ophiobolins in Aspergillus ustus 094102

“…Ophiobolins belong to sesterterpenoids with a 5-8-5 tricyclic skeleton. In total, 112 ophiobolins have been discovered so far [6][7][8][9][10][11][12][13][14][15][16][17][18], most of which are isolated from fungi of the genus Bipolaris and Aspergillus [6]. Ophiobolins show excellent biological activities, especially cytotoxicity.…”