@article{MTMT:34547382,
	title = {Opioid/Dopamine Receptor Binding Studies, NMR and Molecular Dynamics Simulation of LENART01 Chimera, an Opioid-Bombesin-like Peptide},
	url = {https://m2.mtmt.hu/api/publication/34547382},
	author = {Serafin, Pawel and Szeleszczuk, Lukasz and Zhukov, Igor and Szűcs, Edina and Gombos, Dávid and Stefanucci, Azzurra and Mollica, Adriano and Pisklak, Dariusz Maciej and Kleczkowska, Patrycja},
	doi = {10.3390/molecules29010272},
	journal-iso = {MOLECULES},
	journal = {MOLECULES},
	volume = {29},
	unique-id = {34547382},
	issn = {1420-3049},
	abstract = {The design and development of hybrid compounds as a new class of drug candidates remains an excellent opportunity to improve the pharmacological properties of drugs (including enzymatic stability, efficacy and pharmacokinetic and pharmacodynamic profiles). In addition, considering various complex diseases and/or disorders, the conjugate chemistry approach is highly acceptable and justified. Opioids have long been recognized as the most potent analgesics and serve as the basic pharmacophore for potent hybrid compounds that may be useful in pain management. However, a risk of tolerance and physical dependence exists. Since dopamine receptors have been implicated in the aforementioned adverse effects of opioids, the construction of a hybrid with dual action at opioid and dopamine receptors is of interest. Herein, we present nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics simulation results for LENART01, an opioid-ranatensin hybrid peptide. Apart from molecular docking, protein-ligand interactions were also assessed in vitro using a receptor binding assay, which proved LENART01 to be bound to mu-opioid and dopamine receptors, respectively.},
	keywords = {receptor binding; dopamine receptors; Biochemistry & Molecular Biology; hybrid compound},
	year = {2024},
	eissn = {1420-3049},
	orcid-numbers = {Szeleszczuk, Lukasz/0000-0002-5302-3797}
}

@article{MTMT:34407138,
	title = {Synthesis and biochemical evaluation of 17-N-beta-aminoalkyl-4,5α-epoxynormorphinans},
	url = {https://m2.mtmt.hu/api/publication/34407138},
	author = {Ötvös, Ferenc and Szűcs, Edina and Urai, Ákos and Köteles, István and Szabó, Pál Tamás and Varga, Zsuzsanna Katalin and Gombos, Dávid and Hosztafi, Sándor and Benyhe, Sándor},
	doi = {10.1038/s41598-023-46317-3},
	journal-iso = {SCI REP},
	journal = {SCIENTIFIC REPORTS},
	volume = {13},
	unique-id = {34407138},
	issn = {2045-2322},
	abstract = {Opiate alkaloids and their synthetic derivatives are still widely used in pain management, drug addiction, and abuse. To avoid serious side effects, compounds with properly designed pharmacological profiles at the opioid receptor subtypes are long needed. Here a series of 17- N -substituted derivatives of normorphine and noroxymorphone analogues with five- and six-membered ring substituents have been synthesized for structure–activity study. Some compounds showed nanomolar affinity to MOR, DOR and KOR in in vitro competition binding experiments with selective agonists [ 3 H]DAMGO, [ 3 H]Ile 5,6 -deltorphin II and [ 3 H]HS665, respectively. Pharmacological characterization of the compounds in G-protein signaling was determined by [ 35 S]GTPγS binding assays. The normorphine analogues showed higher affinity to KOR compared to MOR and DOR, while most of the noroxymorphone derivatives did not bind to KOR. The presence of 14-OH substituent resulted in a shift in the pharmacological profiles in the agonist > partial agonist > antagonist direction compared to the parent compounds. A molecular docking-based in silico method was also applied to estimate the pharmacological profile of the compounds. Docking energies and the patterns of the interacting receptor atoms, obtained with experimentally determined active and inactive states of MOR, were used to explain the observed pharmacological features of the compounds.},
	year = {2023},
	eissn = {2045-2322},
	orcid-numbers = {Urai, Ákos/0000-0002-7168-3916; Szabó, Pál Tamás/0000-0003-2260-4641; Hosztafi, Sándor/0000-0003-3793-4651}
}

@article{MTMT:34108334,
	title = {Food-inspired peptides from spinach Rubisco endowed with antioxidant, antinociceptive and anti-inflammatory properties},
	url = {https://m2.mtmt.hu/api/publication/34108334},
	author = {Marinaccio, Lorenza and Zengin, Gokhan and Pieretti, Stefano and Minosi, Paola and Szűcs, Edina and Benyhe, Sándor and Novellino, Ettore and Masci, Domiziana and Stefanucci, Azzurra and Mollica, Adriano},
	doi = {10.1016/j.fochx.2023.100640},
	journal-iso = {FOOD CHEM X},
	journal = {FOOD CHEMISTRY: X},
	volume = {18},
	unique-id = {34108334},
	issn = {2590-1575},
	abstract = {Rubiscolin-6 (amino acid sequence: YPLDLF) is a selective & delta;-opioid receptor peptide isolated from spinach Rubisco. Its synthetic analogue, peptide YPMDIV is the most potent described so far for its increased opioid activity, thus in this work it was considered as lead compound for the design of twelve new analogues e.g. LMAS112. Firstly all the novel compounds have been tested for their antinociceptive and anti-inflammatory capacity in vitro and in vivo in order to evaluate their ability to maintain or loss the original activity. Among them peptides LMAS5-8 gave the best results, thus their antioxidant properties have been investigated along with their enzymatic inhibitory ability. Peptide LMAS6 shows a strong antioxidant (154.25 mg TE/g CUPRAC) and inhibitor activity on tyrosinase (84.49 mg KAE/g), indicating a potential role in food industry as anti-browning agent, while peptides LMAS5 and LMAS7 possess a modest cholinesterase inhibitory activity suggesting a conceivable use for nutraceuticals production.},
	keywords = {PURIFICATION; PRODUCTS; PROTEIN; INHIBITORS; ANALOGS; DESIGN; antioxidants; DELTA; rubisco; Chemistry, Applied; bioactive peptides; opioid agonist; Rubiscolin-6; Anti -browning agent},
	year = {2023},
	eissn = {2590-1575},
	orcid-numbers = {Masci, Domiziana/0000-0002-5615-5111; Stefanucci, Azzurra/0000-0001-7525-2913}
}

@article{MTMT:33784924,
	title = {Telmisartan Is a Promising Agent for Managing Neuropathic Pain and Delaying Opioid Analgesic Tolerance in Rats},
	url = {https://m2.mtmt.hu/api/publication/33784924},
	author = {Karádi, Dávid Árpád and Galambos, Anna Rita and Lakatos, Péter Pál and Apenberg, Joost and Abbood, Sarah Kadhim and Balogh, Mihály and Király, Kornél P and Riba, Pál and Gomaa, Nariman Essmat Mohamed Aldeltawab and Szűcs, Edina and Benyhe, Sándor and Varga, Zoltán and Szökő, Éva and Tábi, Tamás and Al-Khrasani, Mahmoud},
	doi = {10.3390/ijms24097970},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {24},
	unique-id = {33784924},
	issn = {1661-6596},
	abstract = {Despite the large arsenal of analgesic medications, neuropathic pain (NP) management is not solved yet. Angiotensin II receptor type 1 (AT1) has been identified as a potential target in NP therapy. Here, we investigate the antiallodynic effect of AT1 blockers telmisartan and losartan, and particularly their combination with morphine on rat mononeuropathic pain following acute or chronic oral administration. The impact of telmisartan on morphine analgesic tolerance was also assessed using the rat tail-flick assay. Morphine potency and efficacy in spinal cord samples of treated neuropathic animals were assessed by [35S]GTPγS-binding assay. Finally, the glutamate content of the cerebrospinal fluid (CSF) was measured by capillary electrophoresis. Oral telmisartan or losartan in higher doses showed an acute antiallodynic effect. In the chronic treatment study, the combination of subanalgesic doses of telmisartan and morphine ameliorated allodynia and resulted in a leftward shift in the dose–response curve of morphine in the [35S]GTPγS binding assay and increased CSF glutamate content. Telmisartan delayed morphine analgesic-tolerance development. Our study has identified a promising combination therapy composed of telmisartan and morphine for NP and opioid tolerance. Since telmisartan is an inhibitor of AT1 and activator of PPAR-γ, future studies are needed to analyze the effect of each component.},
	year = {2023},
	eissn = {1422-0067},
	orcid-numbers = {Lakatos, Péter Pál/0000-0001-6410-0471; Abbood, Sarah Kadhim/0000-0001-5305-8730; Balogh, Mihály/0000-0003-3296-0316; Király, Kornél P/0000-0002-7252-0422; Riba, Pál/0000-0002-7886-4816; Gomaa, Nariman Essmat Mohamed Aldeltawab/0000-0003-3440-6263; Benyhe, Sándor/0000-0002-2235-5334; Varga, Zoltán/0000-0002-2758-0784; Szökő, Éva/0000-0003-1464-6403; Tábi, Tamás/0000-0001-5343-0205; Al-Khrasani, Mahmoud/0000-0001-8488-3266}
}

@article{MTMT:33560486,
	title = {Unique, Specific CART Receptor-Independent Regulatory Mechanism of CART(55-102) Peptide in Spinal Nociceptive Transmission and Its Relation to Dipeptidyl-Peptidase 4 (DDP4)},
	url = {https://m2.mtmt.hu/api/publication/33560486},
	author = {Kozsurek, Márk and Király, Kornél P and Gyimesi, Klára and Lukácsi, Erika and Fekete, Csaba and Gereben, Balázs and Mohácsik, Petra and Helyes, Zsuzsanna and Bölcskei, Kata and Tékus, Valéria and Pap, Károly and Szűcs, Edina and Benyhe, Sándor and Imre, Timea and Szabó, Pál Tamás and Gajtkó, Andrea and Szentesiné Holló, Krisztina and Puskár, Zita},
	doi = {10.3390/ijms24020918},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {24},
	unique-id = {33560486},
	issn = {1661-6596},
	abstract = {Cocaine- and amphetamine-regulated transcript (CART) peptides are involved in several physiological and pathological processes, but their mechanism of action is unrevealed due to the lack of identified receptor(s). We provided evidence for the antihyperalgesic effect of CART(55-102) by inhibiting dipeptidyl-peptidase 4 (DPP4) in astrocytes and consequently reducing neuroinflammation in the rat spinal dorsal horn in a carrageenan-evoked inflammation model. Both naturally occurring CART(55-102) and CART(62-102) peptides are present in the spinal cord. CART(55-102) is not involved in acute nociception but regulates spinal pain transmission during peripheral inflammation. While the full-length peptide with a globular motif contributes to hyperalgesia, its N-terminal inhibits this process. Although the anti-hyperalgesic effects of CART(55-102), CART(55-76), and CART(62-76) are blocked by opioid receptor antagonists in our inflammatory models, but not in neuropathic Seltzer model, none of them bind to any opioid or G-protein coupled receptors. DPP4 interacts with Toll-like receptor 4 (TLR4) signalling in spinal astrocytes and enhances the TLR4-induced expression of interleukin-6 and tumour necrosis factor alpha contributing to inflammatory pain. Depending on the state of inflammation, CART(55-102) is processed in the spinal cord, resulting in the generation of biologically active isoleucine-proline-isoleucine (IPI) tripeptide, which inhibits DPP4, leading to significantly decreased glia-derived cytokine production and hyperalgesia.},
	keywords = {HYPERALGESIA; chronic pain; spinal cord; Allodynia; cocaine- and amphetamine-regulated transcript (CART) peptide; dipeptidyl-peptidase-4 (DPP4)},
	year = {2023},
	eissn = {1422-0067},
	orcid-numbers = {Kozsurek, Márk/0000-0001-5465-2803; Király, Kornél P/0000-0002-7252-0422; Szabó, Pál Tamás/0000-0003-2260-4641}
}

@article{MTMT:33313345,
	title = {The Role of a Natural Amphibian Skin-Based Peptide, Ranatensin, in Pancreatic Cancers Expressing Dopamine D2 Receptors},
	url = {https://m2.mtmt.hu/api/publication/33313345},
	author = {Laskowska, Anna K. and Szudzik, Mateusz and Sciezynska, Aneta and Komorowski, Michal and Szűcs, Edina and Gombos, David and Baczek, Bartlomiej and Lipka-Miciuk, Jowita and Benyhe, Sándor and Kleczkowska, Patrycja},
	doi = {10.3390/cancers14225535},
	journal-iso = {CANCERS},
	journal = {CANCERS},
	volume = {14},
	unique-id = {33313345},
	abstract = {Simple Summary Cancer is one of the most problematic issues worldwide, as it still requires effective therapy. Unfortunately, clinically available cancer-specific medications result in serious side effects. This is also true for pancreatic cancer which additionally is well-known for difficulties in the treatment. Therefore, the aim of the study was to evaluate the biological activity, in terms of anticancer effects, of ranatensin (RAN), a naturally existing bombesin-like peptide. For the first time, we characterized the peptide as a dopaminergic system ligand. However, despite the presence of dopamine receptors in pancreatic cancer cell lines used, RAN was found to affect cancer cells possibly through different receptors since RAN's impact on pancreatic cancer cells was not correlated with their expression level of DRD2. Nevertheless, this peptide may serve as a potential useful agent with therapeutic efficacy in cancers expressing DRD2 receptors, for which DRD2 antagonism is crucial to produce antitumor effects. Despite the progress in early diagnostic and available treatments, pancreatic cancer remains one of the deadliest cancers. Therefore, there is an urgent need for novel anticancer agents with a good safety profile, particularly in terms of possible side-effects. Recently dopaminergic receptors have been widely studied as they were proven to play an important role in cancer progression. Although various synthetic compounds are known for their interactions with the dopaminergic system, peptides have recently made a great comeback. This is because peptides are relatively safe, easy to correct in terms of the improvement of their physicochemical and biological properties, and easy to predict. This paper aims to evaluate the anticancer activity of a naturally existing peptide-ranatensin, toward three different pancreatic cancer cell lines. Additionally, since there is no sufficient information confirming the exact character of the interaction between ranatensin and dopaminergic receptors, we provide, for the first time, binding properties of the compound to such receptors.},
	keywords = {Anticancer agents; Pancreatic cancer; dopamine receptors; ranatensin},
	year = {2022},
	eissn = {2072-6694}
}

@article{MTMT:33221906,
	title = {Discovery of kappa Opioid Receptor (KOR)-Selective D-Tetrapeptides with Improved In Vivo Antinociceptive Effect after Peripheral Administration},
	url = {https://m2.mtmt.hu/api/publication/33221906},
	author = {Stefanucci, Azzurra and Della, Valle Alice and Scioli, Giuseppe and Marinaccio, Lorenza and Pieretti, Stefano and Minosi, Paola and Szűcs, Edina and Benyhe, Sándor and Masci, Domiziana and Tanguturi, Parthasaradhireddy and Chou, Kerry and Barlow, Deborah and Houseknecht, Karen and Streicher, John M. and Mollica, Adriano},
	doi = {10.1021/acsmedchemlett.2c00237},
	journal-iso = {ACS MED CHEM LETT},
	journal = {ACS MEDICINAL CHEMISTRY LETTERS},
	volume = {13},
	unique-id = {33221906},
	issn = {1948-5875},
	abstract = {Peripherally active tetrapeptides as selective kappa opioid receptor (KOR) agonists have been prepared in good overall yields and high purity following solid-phase peptide synthesis via Fmoc protection strategy. Structural modifications at the first and second position of the lead compound FF(D-Nle)R-NH2 (FE200041) were contemplated with aromatic side chains containing D-amino acids, such as (D)-pF-Phe, (D)-mF-Phe, (D)-oF-Phe, which led to highly selective and efficacious KOR agonists endowed with strong antinociceptive activity in vivo following intravenous (i.v.) and subcutaneous (s.c.) administration in the tail flick and formalin tests. These results suggest potential clinical applications in the treatment of neuropathic and inflammatory pain.},
	keywords = {PEPTIDES; SELECTIVITY; BINDING; ANALOGS; AGONIST; DESIGN; NOCICEPTION; MU; PROFILE; BIOLOGICAL EVALUATION; biphalin; TAIL FLICK; Kappa opioid receptors},
	year = {2022},
	pages = {1707-1714},
	orcid-numbers = {Stefanucci, Azzurra/0000-0001-7525-2913}
}

@article{MTMT:33174887,
	title = {Non-genomic uterorelaxant actions of corticosteroid hormones in rats: An in vitro and in vivo study},
	url = {https://m2.mtmt.hu/api/publication/33174887},
	author = {Mirdamadi, Seyedmohsen and Schaffer, Annamária and Barna, Tamara and Samavati, Reza and Szűcs, Kálmán Ferenc and Szűcs, Edina and Benyhe, Sándor and Szécsi, Mihály and Gáspár, Róbert},
	doi = {10.1016/j.ejphar.2022.175346},
	journal-iso = {EUR J PHARMACOL},
	journal = {EUROPEAN JOURNAL OF PHARMACOLOGY},
	volume = {935},
	unique-id = {33174887},
	issn = {0014-2999},
	year = {2022},
	eissn = {1879-0712},
	orcid-numbers = {Szécsi, Mihály/0000-0002-4272-1362; Gáspár, Róbert/0000-0002-1571-7579}
}

@article{MTMT:32624010,
	title = {Fentanyl but Not Morphine or Buprenorphine Improves the Severity of Necrotizing Acute Pancreatitis in Rats},
	url = {https://m2.mtmt.hu/api/publication/32624010},
	author = {Bálint, Emese Réka and Fűr, Gabriella and Kui, Balázs and Balla, Zsolt and Kormányos, Eszter Sára and Orján, Erik Márk and Tóth, Brigitta and Horváth, Gyöngyi and Szűcs, Edina and Benyhe, Sándor and Ducza, Eszter and Pallagi, Petra and Maléth, József and Venglovecz, Viktória and Hegyi, Péter and Kiss, Lóránd and Rakonczay, Zoltán},
	doi = {10.3390/ijms23031192},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {23},
	unique-id = {32624010},
	issn = {1661-6596},
	abstract = {Opioids are widely used for the pain management of acute pancreatitis (AP), but their impact on disease progression is unclear. Therefore, our aim was to study the effects of clinically relevant opioids on the severity of experimental AP. Various doses of fentanyl, morphine, or buprenorphine were administered as pre- and/or post-treatments in rats. Necrotizing AP was induced by the intraperitoneal injection of L-ornithine-HCl or intra-ductal injection of Na-taurocholate, while intraperitoneal caerulein administration caused edematous AP. Disease severity was determined by laboratory and histological measurements. Mu opioid receptor (MOR) expression and function was assessed in control and AP animals. MOR was expressed in both the pancreas and brain. The pancreatic expression and function of MOR were reduced in AP. Fentanyl post-treatment reduced necrotizing AP severity, whereas pre-treatment exacerbated it. Fentanyl did not affect the outcome of edematous AP. Morphine decreased vacuolization in edematous AP, while buprenorphine pre-treatment increased pancreatic edema during AP. The overall effects of morphine on disease severity were negligible. In conclusion, the type, dosing, administration route, and timing of opioid treatment can influence the effects of opioids on AP severity. Fentanyl post-treatment proved to be beneficial in AP. Clinical studies are needed to determine which opioids are best in AP.},
	keywords = {MORPHINE; ANALGESIA; fentanyl; Acute pancreatitis; Opioids; buprenorphine},
	year = {2022},
	eissn = {1422-0067},
	orcid-numbers = {Kormányos, Eszter Sára/0000-0002-6201-1341; Orján, Erik Márk/0000-0003-4176-0834; Horváth, Gyöngyi/0000-0002-6025-4577; Pallagi, Petra/0000-0001-8906-0840; Maléth, József/0000-0001-5768-3090; Venglovecz, Viktória/0000-0002-2316-7247; Hegyi, Péter/0000-0003-0399-7259; Rakonczay, Zoltán/0000-0002-1499-3416}
}

@mastersthesis{MTMT:32475872,
	title = {Comparative biochemical and pharmacological investigations of various newly developed opioid receptor ligands [Különböző újonnan kifejlesztett opioid receptor ligandok összehasonlító biokémiai és farmakológiai vizsgálata]},
	url = {https://m2.mtmt.hu/api/publication/32475872},
	author = {Szűcs, Edina},
	doi = {10.14232/phd.10631},
	publisher = {SZTE},
	unique-id = {32475872},
	year = {2021}
}