Semi-synthetic derivatives of natural isoflavones from Maclura pomifera as a novel class of PDE-5A inhibitors

Ribaudo, Giovanni; Pagano, Mario A.; Pavan, Valeria; Redaelli, Marco; Zorzan, Maira; Pezzani, Raffaele; Mucignat‐Caretta, Carla; Vendrame, Tiziano; Bova, Sergio; Zagotto, Giuseppe

doi:10.1016/j.fitote.2015.06.020

Cited by 27 publications

(24 citation statements)

References 25 publications

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“…Moreover, the introduction of the -SO 2 -group provides to compound 2 further structural similarity with sildenafil, the well-known PDE5 inhibitor. Moreover, this hypothesis was supported by our previous experimental evidences which suggest that the protections/substitution of hydroxyl groups in the isoflavone scaffold may lead to a highest inhibitory activity (lower IC 50 ) towards PDE5 in vitro [8]. The preparation of the methanesulfonate derivative of osajin (1) was straightforwardly carried out adopting and modifying a procedure described by Wolfrom et al [15].…”

Section: Extraction Of Osajin (1) and Synthesis Ofmentioning

confidence: 68%

“…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]. Thus, 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.…”

Section: Introductionmentioning

confidence: 89%

“…Besides for its activity on PDE5, the prenylated isoflavone osajin (1) has also been studied as an antioxidant, an anticancer and antibacterial agent [11][12][13]. The extraction of osajin (1) was performed according to a procedure that we previously reported [8,9]. Briefly, the compound was isolated from the dried fruits using a soxhlet apparatus.…”

Section: Extraction Of Osajin (1) and Synthesis Ofmentioning

confidence: 99%

“…Docking results and interaction poses were analyzed and visualized with Chimera [16]. The docking experiments were performed on osajin (1), compound 2, and sildenafil as a reference in accordance to our previous in silico studies on the same target [8].…”

Section: In Silico Studiesmentioning

confidence: 99%

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

Ribaudo

Ongaro

Zagotto

2018

Molbank

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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.

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Section: Extraction Of Osajin (1) and Synthesis Ofmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 89%

Section: Extraction Of Osajin (1) and Synthesis Ofmentioning

confidence: 99%

Section: In Silico Studiesmentioning

confidence: 99%

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

Ribaudo

Ongaro

Zagotto

2018

Molbank

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“…The vasorelaxant properties of silymarin flavonolignans were addressed ex vivo on isolated rat aorta. This is a classical experimental model widely used in basic pharmacological research [30,33,34]. The parent flavonolignans were studied first.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Silymarin Flavonolignans and Their Sulfated Conjugates on Platelet Aggregation and Blood Vessels Ex Vivo

et al. 2019

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Silymarin is a traditional drug and food supplement employed for numerous liver disorders. The available studies indicate that its activities may be broader, in particular due to claimed benefits in some cardiovascular diseases, but the contributions of individual silymarin components are unclear. Therefore, we tested silymarin flavonolignans as pure diastereomers as well as their sulfated metabolites for potential vasorelaxant and antiplatelet effects in isolated rat aorta and in human blood, respectively. Eleven compounds from a panel of 17 tested exhibited a vasorelaxant effect, with half maximal effective concentrations (EC50) ranging from 20 to 100 µM, and some substances retained certain activity even in the range of hundreds of nM. Stereomers A were generally more potent as vasorelaxants than stereomers B. Interestingly, the most active compound was a metabolite—silychristin-19-O-sulfate. Although initial experiments showed that silybin, 2,3-dehydrosilybin, and 2,3-dehydrosilychristin were able to substantially block platelet aggregation, their effects were rapidly abolished with decreasing concentration, and were negligible at concentrations ≤100 µM. In conclusion, metabolites of silymarin flavonolignans seem to have biologically relevant vasodilatory properties, but the effect of silymarin components on platelets is low or negligible.

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Chemical composition and antimicrobial activity of Osage orange (Maclura pomifera) leaf extracts

Filip

Đurović

Blagojević

et al. 2020

Archiv der Pharmazie

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The main goal of this study was to establish the chemical profile of Osage orange (Maclura pomifera) leaf extracts, obtained by conventional maceration technique, and to examine its antimicrobial activity. The identification and quantification of the extract compounds were done using ultra‐high‐performance liquid chromatography, with a diode array detector coupled with triple‐quadrupole mass spectrometer and gas chromatography–mass spectrometry techniques. Thirty‐one polyphenolic compounds were detected and identified in the ethanolic extracts, whereby 5‐O‐caffeoylquinic acid was found to be the dominant compound. Among other compounds, pentacosane and palmitic acid were the most abundant compounds in the dichloromethane extract. The preliminary antimicrobial activity screening shows that Gram‐positive bacteria tend to be more sensitive to the investigated extracts. The highest antimicrobial activity was determined against Enterococcus faecalis ATCC 19433 and Listeria monocytogenes ATCC 35152. From these results, Osage orange leaves can be considered as plant material with significant antimicrobial properties.

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Semi-synthetic derivatives of natural isoflavones from Maclura pomifera as a novel class of PDE-5A inhibitors

Cited by 27 publications

References 25 publications

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

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

The Effect of Silymarin Flavonolignans and Their Sulfated Conjugates on Platelet Aggregation and Blood Vessels Ex Vivo

Chemical composition and antimicrobial activity of Osage orange (Maclura pomifera) leaf extracts

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