Biological macromolecule binding and anticancer activity of synthetic alkyne-containing l-phenylalanine derivatives

Fik-Jaskółka, Marta A.; Mkrtchyan, Anna F.; Saghyan, Ashot S.; Palumbo, Rosanna; Belter, Agnieszka; Hayriyan, Liana A.; Simonyan, Hayarpi; Roviello, Valentina; Roviello, Giovanni N.

doi:10.1007/s00726-020-02849-w

Cited by 16 publications

(12 citation statements)

References 89 publications

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“…the main protease M pro (PDB ID: 6YB4), was obtained from Protein Data Bank (Berman et al 2002 ). The 2D structures for the ligands were retrieved from PubChem database ( https://pubchem.ncbi.nlm.nih.gov/ ), while those not available in PubChem were drawn using the molecular editor provided in 1-Click Mcule (Mcule Inc., Palo Alto, CA, USA) (Potemkin et al 2019 ; Fik-Jaskółka et al 2020a , b , a; Kiss et al 2012 ), a web-based platform powered by AutoDock Vina docking algorithm (Trott and Olson 2009 ) by which we realized our docking experiments. The atomic coordinates of the binding site were those reported in the recent literature (Umesh et al 2020 ) ( X : 9.204, Y : − 4.557 and Z : 19.602), and the size of the binding site was 22 Angstrom.…”

Section: Methodsmentioning

confidence: 99%

Lower COVID-19 mortality in Italian forested areas suggests immunoprotection by Mediterranean plants

Roviello

2020

Environ Chem Lett

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The COVID-19 pandemic has induced dramatic effects on the population of the industrialized north of Italy, whereas it has not heavily affected inhabitants of the southern regions. This might be explained in part by human exposure to high levels of fine particulate matter (PM) in the air of northern Italy, thus exacerbating the mortality. Since trees mitigate air pollution by intercepting PM onto plant surfaces and bolster the human immune system by emitting bioactive volatile organic compounds (VOCs), we hypothesize a protective role of evergreen forested areas in southern Italy. We compared the mortality rate due to COVID-19, the death number, the positivity rate and the forest coverage per capita in various Italian regions. Hectares of forest per capita and prevalence of deciduous versus evergreen forestal species were also estimated. In silico docking studies of potentially protective compounds found in Laurus nobilis L., a typical Mediterranean plant, were performed to search for potential antivirals. We found that the pandemic's severity was generally lower in southern regions, especially those with more than 0.3 hectares of forest per capita. The lowest mortality rates were found in southern Italy, mainly in regions like Molise (0.007%) and Basilicata (0.005%) where the forest per capita ratio is higher than 0.5 Ha/person. Our findings suggest that evergreen Mediterranean forests and shrubland plants could have protected the southern population by emission of immunomodulating VOCs and provision of dietary sources of bioactive compounds. Moreover, in silico studies revealed a potential anti-COVID-19 activity in laurusides, which are unexplored glycosides from bay laurel. Overall, our results highlight the importance of nature conservation and applications to the search for natural antivirals.

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Section: Methodsmentioning

confidence: 99%

Lower COVID-19 mortality in Italian forested areas suggests immunoprotection by Mediterranean plants

Roviello

2020

Environ Chem Lett

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Section: Methodsmentioning

confidence: 99%

“…Both cell viability and proliferation were measured by MTT colorimetric assay [48,49]. For cell viability, VSMCs were plated in 96-well plates (1 × 10 4 cells/well) and allowed to attach overnight at 37 • C, then incubated overnight in serum-free media at 37 • C. PS5 and NC peptides were then added to the plate (25 µM) and incubated for an additional 6 h in DMEM containing 0.5% FBS, using a medium with 10% FBS as the positive control.…”

Section: Cell Viability Proliferation and Migrationmentioning

confidence: 99%

Antioxidant Effects of PS5, a Peptidomimetic of Suppressor of Cytokine Signaling 1, in Experimental Atherosclerosis

et al. 2020

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The chronic activation of the Janus kinase/signal transducer and activator of the transcription (JAK/STAT) pathway is linked to oxidative stress, inflammation and cell proliferation. Suppressors of cytokine signaling (SOCS) proteins negatively regulate the JAK/STAT, and SOCS1 possesses a small kinase inhibitory region (KIR) involved in the inhibition of JAK kinases. Several studies showed that KIR-SOCS1 mimetics can be considered valuable therapeutics in several disorders (e.g., diabetes, neurological disorders and atherosclerosis). Herein, we investigated the antioxidant and atheroprotective effects of PS5, a peptidomimetic of KIR-SOCS1, both in vitro (vascular smooth muscle cells and macrophages) and in vivo (atherosclerosis mouse model) by analyzing gene expression, intracellular O2•− production and atheroma plaque progression and composition. PS5 was revealed to be able to attenuate NADPH oxidase (NOX1 and NOX4) and pro-inflammatory gene expression, to upregulate antioxidant genes and to reduce atheroma plaque size, lipid content and monocyte/macrophage accumulation. These findings confirm that KIR-SOCS1-based drugs could be excellent antioxidant agents to contrast atherosclerosis.

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“…For the computational studies, we used the 3D structure of M pro with an unliganded active site (PDB ID: 6Y84), downloaded from the Protein Data Bank [40]. The structures for the natural compounds (Figure 2) investigated as protease ligands were retrieved by us from the PubChem database (https://pubchem.ncbi.nlm.nih.gov/, all links mentioned in this work were accessed on 11 December 2020), whilst those not present in PubChem were drawn with the molecular editor of 1-Click Mcule (Mcule Inc., Palo Alto, CA, USA) [41][42][43][44], an online docking platform making use of AutoDock Vina [45], by which the docking experiments herein described were performed. For the molecular dockings, we used, as atomic coordinates of the binding site, X: 9.204, Y: −4.557, and Z: 19.602, which were previously reported in the literature for the binding center [46], and we set the size of the binding site as 22 Angstrom.…”

Section: Molecular Docking Studiesmentioning

confidence: 99%

In Silico Investigation on the Interaction of Chiral Phytochemicals from Opuntia ficus-indica with SARS-CoV-2 Mpro

Vicidomini

Roviello

2021

Symmetry

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Opuntia ficus-indica is a cactaceous plant native to America but, nowadays, widely found worldwide, having been the most common domesticated species of cactus grown as a crop plant in semiarid and arid parts of the globe, including several Mediterranean basin countries. Opuntia ficus-indica can be regarded as a medicinal plant, being source of numerous bioactive phytochemicals such as vitamins, polyphenols, and amino acids. The urgent need for therapeutic treatments for the COronaVIrus Disease 19 (COVID-19), caused by the Severe Acute Respiratory Syndrome (SARS)-Coronavirus (CoV)-2, justifies the great attention currently being paid not only to repurposed antiviral drugs, but also to natural products and herbal medications. In this context, the anti-COVID-19 utility of Opuntia ficus-indica as source of potential antiviral drugs was investigated in this work on the basis of the activity of some of its phytochemical constituents. The antiviral potential was evaluated in silico in docking experiments with Mpro, i.e., the main protease of SARS-CoV-2, that is one of the most investigated protein targets of therapeutic strategies for COVID-19. By using two web-based molecular docking programs (1-Click Mcule and COVID-19 Docking Server), we found, for several flavonols and flavonol glucosides isolated from Opuntia ficus-indica, good binding affinities for Mpro, and in particular, binding energies lower than −7.0 kcal/mol were predicted for astragalin, isorhamnetin, isorhamnetin 3-O-glucoside, 3-O-caffeoyl quinic acid, and quercetin 5,4′-dimethyl ether. Among these compounds, the chiral compound astragalin showed in our in silico studies the highest affinity for Mpro (−8.7 kcal/mol) and also a low toxicity profile, emerging, thus, as an interesting protease inhibitor candidate for anti-COVID-19 strategies.

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Biological macromolecule binding and anticancer activity of synthetic alkyne-containing l-phenylalanine derivatives

Cited by 16 publications

References 89 publications

Lower COVID-19 mortality in Italian forested areas suggests immunoprotection by Mediterranean plants

Lower COVID-19 mortality in Italian forested areas suggests immunoprotection by Mediterranean plants

Antioxidant Effects of PS5, a Peptidomimetic of Suppressor of Cytokine Signaling 1, in Experimental Atherosclerosis

In Silico Investigation on the Interaction of Chiral Phytochemicals from Opuntia ficus-indica with SARS-CoV-2 Mpro

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