5-Hydroxy-3-(4-hydroxyphenyl)-8,8-dimethyl-6-(3-methylbut-2-enyl)pyrano[2,3-h]chromen-4-one

Abstract

Natural and semi-synthetic compounds are being studied as novel phosphodiesterase 5 (PDE5) inhibitors for the treatment of erectile dysfunction, pulmonary hypertension, and lower urinary symptoms. Maclura pomifera is a source of flavonoids, one of the main classes of molecules investigated for these purposes. The extraction of the natural isoflavone osajin and its modification to obtain a semi-synthetic derivative are described in this short note. 1 H and 13 C-nuclear magnetic resonance spectroscopy (NMR), mass spectrometry, high-performance liquid chromatography (HPLC) and spectroscopic characterization of the title compound are also hereby provided. Two-dimensional (2D) nuclear Overhauser effect spectroscopy (NOESY) NMR, supported by in silico conformational studies, was used to achieve a complete assignment of the proton signals, assessing the correct chemical structure of the compound. Heteronuclear single quantum coherence spectroscopy (HSQC) and heteronuclear multiple bond correlation (HMBC) NMR experiments were performed to assign 13 C chemical shifts. Calculated chemical properties and preliminary in silico docking suggest that this molecule might be a promising candidate as PDE5 inhibitor.

Antioxidant Activity of Osage Orange Extract in Soybean Oil and Fish Oil during Storage

“…However, the contents of osajin and pomiferin were not reported in these studies. Extraction methods using petroleum ether (Wolfrom and Mahan, 1942) and diethyl ether (Ribaudo et al, 2018) followed by the formation of lead complexes, separation, and removal of lead were also developed to produce pure osajin and pomiferin.…”

A Perspective on Natural and Nature-Inspired Small Molecules Targeting Phosphodiesterase 9 (PDE9): Chances and Challenges against Neurodegeneration

“…Flavonoids are among the most widely studied classes of natural PDE inhibitors, even if the great majority of contributions in the literature are focused on the evaluation of such compounds against PDE5 [ 8 , 32 , 33 , 34 , 35 ]. Concerning this class, hesperidin and naringenin were reported to induce relaxing effects of noradrenaline-, okadaic acid-, and KCl-precontracted aorta.…”

2-(3,4-Dihydroxyphenyl)-4-(2-(4-nitrophenyl)hydrazono)-4H-chromene-3,5,7-triol

“…Quercetin was previously reported to possess inhibitory activity on several PDE isoforms [24], and the vasorelaxant effect of this natural flavonoid and of the corresponding metabolites was demonstrated to be due to the interference with the cGMP pathway [25]. Chan et al investigated the effects of quercetin derivatives on PDE isoforms [26], and we previously explored the semi-synthetic derivatization of flavonoids to enhance their interaction with PDE5 in silico and in vitro [21,22].…”

“…The interaction of compound 1 with PDE5 was investigated in silico following a protocol reported previously [22]. For comparison, sildenafil and quercetin were also docked to the same 3D model and the predicted interaction patterns demonstrated a good co-localization of the ligands within the protein.…”

“…Flavonoids, in particular, have been known as PDE inhibitors for decades [15]. Natural glycosylated flavonoids and aglycones [16][17][18][19], as well as semi-synthetic flavones [20] and isoflavones [21][22][23], have been studied in silico, in vitro and in vivo for their inhibitory activity towards PDE5 and other isoforms.…”