Eremophilane Sesquiterpenoids with Antibacterial and Anti-inflammatory Activities from the Endophytic Fungus Septoria rudbeckiae

Abstract

Fourteen eremophilane sesquiterpenoids (1–14), including nine new congeners, septoreremophilanes A–I (1–9), together with three known sesquiterpenes (15–17), two known tetralone derivatives (18, 19), and two known cholesterol analogues (20, 21), were isolated from the endophytic fungus Septoria rudbeckiae. Compounds 1–6 and 7a belong to the family of the highly oxygenated eremophilane sesquiterpenoids with a 6/6/5 tricyclic system and bearing a hemiacetal moiety. The inhibitions of all metabolites against eight bacteria were estimated in vitro, and nine new metabolites (1–9) were tested for antineuroinflammatory activity. Notably, the effects of 4 against Pseudomonas syringae pv. actinidae and 20 against Bacillus cereus displayed potent inhibitory, with the MIC values of 6.25 and 6.25 μM, respectively. Further, scanning electron microscopy analyses indicated that 4 and 20 were to change the outer configuration of bacterial cells, respectively, and the investigations demonstrated that 4 and 20 may act as potential structure templates for the development of the agrochemical bactericides. Additionally, compound 6 displayed potent inhibition of NO generation in lipopolysaccharide-induced BV-2 microglial cells (IC50 = 12.0 ± 0.32 μM), and the conceivable anti-inflammatory mechanisms implicated were also investigated by molecular docking. Thus, the bioactive metabolites of the strain S. rudbeckiae may serve as a novel resource to be developed.

Cumulative Data of 1H and 13C NMR Signals and Specific Rotations of Eremophilane Sesquiterpenoids. 1. Bicyclic Eremophilanes (1)

“…Septoreremophilane G has C-14α and C-15α absolute configurations and exists as a mixture of open form 177 and cyclized form 178 in a ratio of 1:1.3 in methanol. 62 The H 2 -12 of the open form 177 resonating at δ 4.06 (q, J = 14.4 Hz) seems an AB quartet. Cyclized form of septoreremophilane G ( 178 ) is a tricyclic eremophilane and should be listed in the later chapter; however, this is one of the equilibrium isomers and, therefore, shown in Table 23.…”

“…The CD spectra of compounds 305-307 and setoreremophilane H (315) were measured. 62,92,155 Table 36 includes the data of seven carboxylic acids, 316-322, and methyl ester 323 (Figure 15). Compound 323 is the corresponding methyl ester of 322.…”

Discovery of diversified cassane diterpenoids as potent antibacterial agents from Caesaplinia pulcherrima and their mechanisms

“…The minimal inhibitory concentration (MIC) is an indicator of the antibacterial properties of compounds as described by the National Committee for Clinical Laboratory Standards 21 . The MIC values of compounds were determined by a microbroth dilution method in 96‐well flat microtiter plates as described previously in the antibacterial activity tests 22 . The bacterial fluid was fostered in the LB medium (10 g of tryptone, 5 g of yeast extract power, 10 g of NaCl, dissolved in 1 L of deionized water) to 10 6 CFU mL −1 .…”

“…21 The MIC values of compounds were determined by a microbroth dilution method in 96-well flat microtiter plates as described previously in the antibacterial activity tests. 22 The bacterial fluid was fostered in the LB medium (10 g of tryptone, 5 g of yeast extract power, 10 g of NaCl, dissolved in 1 L of deionized water) to 10 6 CFU mL −1 . Then, the bacterial suspension (100 μL, 2 × 10 6 CFU mL −1 ) and 100 μL of compound solutions at different concentrations (3.125, 6.25, 12.5, 50, 100 μM) were added into the 96-well plate.…”

“…The growth curves of compounds 1 and 3 against Psa, B. cereus, and S. aureus were assessed according to a modified version of the reported method. 22 In the 96-well plate, 100 μL of the above bacterial suspension (10 6 CFU mL −1 ) and 100 μL of different concentrations (ultima densities of 1/2 × MIC, 3/4 × MIC, and 1 × MIC) of samples solutions were incubated at 37 °C. An equivalent volume of DMSO was used as the blank control.…”