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. 1H and 13C-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 13C chemical shifts. Calculated chemical properties and preliminary in silico docking suggest that this molecule might be a promising candidate as PDE5 inhibitor.
Highlights
The inhibitors of phosphodiesterase 5 (PDE5) are currently used in the clinical practice for the treatment of erectile dysfunction, pulmonary hypertension, and lower urinary symptoms [1], but several other potential therapeutic applications are emerging [1,2]
Calculated chemical properties and preliminary in silico docking suggest that this molecule might be a promising candidate as PDE5 inhibitor
Scientific literature is prolific for what concerns natural compounds or nature-inspired molecules showing inhibitory activity on PDE5 [3,4,5,6]
Summary
The inhibitors of phosphodiesterase 5 (PDE5) are currently used in the clinical practice for the treatment of erectile dysfunction, pulmonary hypertension, and lower urinary symptoms [1], but several other potential therapeutic applications are emerging [1,2]. Flavonoids extracted from plants are among the most well-studied compounds in this context [3,4,7]. We previously reported the positive in silico and in vitro results of our studies on natural isoflavones from Maclura pomifera and their semi-synthetic derivatives as PDE5 inhibitors [8,9]. We improved the extraction conditions of the natural scaffold and expanded the variety of chemical modifications with the aim of further improving the efficacy against PDE5. The procedures for the extraction of osajin (1) from Maclura pomifera and the reaction conditions for the isolation of compound 2 are here described. NMR, mass spectrometry, HPLC and ultra-violet (UV) data are reported. Particular attention was dedicated to the complete assignment of the proton and 13 C-NMR signals, achieved by using 2D NOESY, heteronuclear single quantum coherence spectroscopy (HSQC) and heteronuclear multiple bond correlation (HMBC) experiments
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