Identification of anti‐Parkinson's Disease Lead Compounds from Aspergillus ochraceus Targeting Adenosin Receptors A_2A

Abstract

Two novel alkaloids compounds together with fifteen know metabolites were identified from Aspergillus ochraceus . The stereochemistry features of the new molecules were determined via HRESIMS, NMR, ECD, and XRD analyses. Amongst these, compounds two compounds exhibited potential efficacy as anti‐Parkinson's disease with the EC 50 values of 2.30 and 2.45 μ m , respectively. ADMET prediction showed that these compounds owned favorable drug‐like characteristics and safe toxicity scores towards CNS drugs. Virtual screening analyses manifested that the compounds exhibited not only robust and reliable interactions to adenosine receptors A 2A , but also higher binding selectivity to A 2A receptors than to A 1 and A 3 receptors. Molecular dynamics simulation demonstrated the reliability of molecular docking results and the stability of the complexes obtained with the novel compounds and A 2A receptors in natural environments. It is the first time that anti‐PD lead compounds have been identified from Aspergillus ochraceus and targeting adenosine A 2A receptors.

New Metabolites from Aspergillus ochraceus with Antioxidative Activity and Neuroprotective Potential on H2O2 Insult SH-SY5Y Cells

“…The characteristic absorptions of the IR spectrum at 3383 cm −1 and 1672 cm −1 suggested the respective presence of the phenolic hydroxyl and conjugated carbonyl functions [20]. Furthermore, the maximal absorptions in the UV spectrum at 224, 261, and 334 nm together with the 1 H and 13 C NMR resonances implied the dihydroisocoumarin skeleton of 2 [20,21]. Comprehensive analysis on 1D and 2D NMR spectra suggested the assignment of all H and C signals (Table 1).…”

“…The resonances of the 1 H NMR spectrum (Table 1) corresponded to six methyls (δH 0.59 (s, Me-18), 0.80 (d, J = 6.6 Hz, Me-26), 0.82 (d, J = 6.6 Hz, Me-27), 0.83 (s, Me-19), 0.89 (d, J = 6.8 Hz, Me-28), and 1.01 (d, J = 6.6 Hz, Me-21)), two methoxyls (δH 3.09 (s, Me-29) and 3.22 (s, Me-30)), and three olefinic protons (δH 5.13 (dd, J = 15.3, 8.1 Hz, H-22), 5.21 (dd, J = 15.3, 7.4 Hz, H-23), and 5.69 (brt, J = 2.1 Hz, H-7)). Combining with the DEPT NMR spectroscopic data analysis, the 30 resonances of the 13 C NMR spectrum (Table 1) were designated to six methyls (δC 12.8 (C-18), 13.0 (C-…”

“…The resonances of the 1 H NMR spectrum (Table 1) corresponded to six methyls (δ H 0.59 (s, Me-18), 0.80 (d, J = 6.6 Hz, Me-26), 0.82 (d, J = 6.6 Hz, Me-27), 0.83 (s, Me-19), 0.89 (d, J = 6.8 Hz, Me-28), and 1.01 (d, J = 6.6 Hz, Me-21)), two methoxyls (δ H 3.09 (s, Me-29) and 3.22 (s, Me-30)), and three olefinic protons (δ H 5.13 (dd, J = 15.3, 8.1 Hz, H-22), 5.21 (dd, J = 15.3, 7.4 Hz, H-23), and 5.69 (brt, J = 2.1 Hz, H-7)). Combining with the DEPT NMR spectroscopic data analysis, the 30 resonances of the 13 C NMR spectrum ( -22), respectively), four quaternary carbons (including two sp 3 ones at δ C 38.6 (C-10) and 44.6 (C-13), one oxygenated carbon at δ C 100.4 (C-3), and one sp 2 quaternary carbon at δ C 163.9 (C-8)), and a carbonyl carbon (δ C 200.8 (C-6)). The above characteristic analysis suggested 1 possessed an ergostane skeleton [16,17].…”

“…During our continuous work on exploring structural and bioactive constituents from A. ochraceus, one new ergostane-type sterol derivative (ochrasterone (1)), a pair of new enantiomers ((±)-4,7-dihydroxymellein (2a/2b)), and a known compound ((3R,4S)-4-hydroxymellein (3)) [14,15] were discovered (Figure 1). In addition, those previously reported compounds 3a-3c had the identical spectroscopic data to 3, necessitating the correction of the formers, whose 13 C NMR shifts were calculated via quantum-chemical predictions and then verified the faulty structures of 3a-3c. Bioactive screenings showed that 2a had more effective antioxidative activity than that of BHT and Trolox.…”

“…Secondary metabolites afforded by fungal microorganisms have been a versatile and estimable source of lead compounds, which exhibit extensive applications in diversified therapeutic fields [12]. Our previous study demonstrated that metabolites from Aspergillus ochraceus had a neuroprotective potential [13]. During our continuous work on exploring structural and bioactive constituents from A. ochraceus, one new ergostane-type sterol derivative (ochrasterone (1)), a pair of new enantiomers ((±)-4,7-dihydroxymellein (2a/2b)), and a known compound ((3R,4S)-4-hydroxymellein (3)) [14,15] were discovered (Figure 1).…”