TY - JOUR AU - Bauder-Wuest, Ulrike AU - Schaefer, Martin AU - Winter, Ruth AU - Remde, Yvonne AU - Roscher, Mareike AU - Breyl, Heinz AU - Poethko, Thorsten AU - Tömböly, Csaba AU - Benesova-Schaefer, Martina TI - Synthesis of tritium-labeled Lu-PSMA-617: Alternative tool for biological evaluation of radiometal-based pharmaceuticals JF - APPLIED RADIATION AND ISOTOPES J2 - APPL RADIAT ISOTOPES VL - 197 PY - 2023 PG - 12 SN - 0969-8043 DO - 10.1016/j.apradiso.2023.110819 UR - https://m2.mtmt.hu/api/publication/34043898 ID - 34043898 AB - This project focuses on the generation and evaluation of functional alternatives to radiometal-based pharmaceuticals supporting basic research and the in vitro developmental phase. Employing robust tritium chemistry and non-radioactive metal surrogates in two synthetic and labeling strategies resulted in ([ring-3H]Nal)PSMA-617 and ([alpha,ss-3H]Nal)PSMA-617. In particular, ([alpha,ss-3H]Nal)Lu-PSMA-617 exhibited high radiolytic as well as metalcomplex stability and was compared to the clinically-established radiopharmaceutical [177Lu]Lu-PSMA-617. The cell-based assays confirmed the applicability of ([alpha,ss-3H]Nal)Lu-PSMA-617 as a substitute of [177Lu]Lu-PSMA617 in pre-clinical biological settings. LA - English DB - MTMT ER - TY - JOUR AU - Dvorácskó, Szabolcs AU - Körmöczi, Tímea AU - Sija, Éva AU - Bende, Balázs AU - Weiczner, Roland AU - Varga, Tibor AU - Ilisz, István AU - Institóris, László AU - Kereszty, Éva Margit AU - Tömböly, Csaba AU - Berkecz, Róbert TI - Focusing on the 5F-MDMB-PICA, 4F-MDMB-BICA synthetic cannabinoids and their primary metabolites in analytical and pharmacological aspects JF - TOXICOLOGY AND APPLIED PHARMACOLOGY J2 - TOXICOL APPL PHARM VL - 470 PY - 2023 PG - 10 SN - 0041-008X DO - 10.1016/j.taap.2023.116548 UR - https://m2.mtmt.hu/api/publication/33831570 ID - 33831570 N1 - TKP2021-EGA LA - English DB - MTMT ER - TY - JOUR AU - Dvorácskó, Szabolcs AU - Dimmito, Marilisa Pia AU - Sebastiani, Jessica AU - La, Regina Giuseppe AU - Silvestri, Romano AU - Pieretti, Stefano AU - Stefanucci, Azzurra AU - Tömböly, Csaba AU - Mollica, Adriano TI - Rimonabant-Based Compounds Bearing Hydrophobic Amino Acid Derivatives as Cannabinoid Receptor Subtype 1 Ligands JF - ACS MEDICINAL CHEMISTRY LETTERS J2 - ACS MED CHEM LETT VL - 14 PY - 2023 IS - 4 SP - 479 EP - 486 PG - 8 SN - 1948-5875 DO - 10.1021/acsmedchemlett.3c00024 UR - https://m2.mtmt.hu/api/publication/33723359 ID - 33723359 N1 - Funding Agency and Grant Number: ACKNOWLEDGMENTS Sapienza University of Rome [RG11816428A9B4D5, RM120172A7EAD07C, RM11916B5598E3C4, AR12117A8A6E80F0, UNKP-21-4-Szte-127]; Sapienza University of Rome [RG11816428A9B4D5, RM120172A7EAD07C, RM11916B5598E3C4, AR12117A8A6E80F0]; New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund [UNKP-21-4-Szte-127]; National Research, Development and Innovation Office [K124952] Funding text: Sapienza University of Rome RG11816428A9B4D5 and RM120172A7EAD07C to R.S., RM11916B5598E3C4 to G.L., and AR12117A8A6E80F0 to J.S. This research was supported by the UNKP-21-4-Szte-127 New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund. S.D. and C.T. were supported by grant K124952 from the National Research, Development and Innovation Office. AB - In this study, 1H-pyrazole-3-carboxylic acids related to the cannabinoid type 1 (CB1) receptor antagonist rimonabant were amidated with valine or tert-leucine, and the resulting acids were further diversified as methyl esters, amides, and N-methyl amides. In vitro receptor binding and functional assays demon-strated a wide series of activities related to the CB1 receptors (CB1Rs). Compound 34 showed a high CB1R binding affinity (Ki = 6.9 nM) and agonist activity (EC50 = 46 nM; Emax = 135%). Radioligand binding and [35S]GTP gamma S binding assays also demonstrated its selectivity and specificity to CB1Rs. Moreover, in vivo experiments revealed that 34 was slightly more effective than the CB1 agonist WIN55,212-2 in the early phase of the formalin test, indicating a short duration of the analgesic effect. Interestingly, in a mouse model of zymosan-induced hindlimb edema, 34 was able to maintain the percentage of paw volume below 75% for 24 h following subcutaneous injection. After intraperitoneal administration, 34 increased the food intake of mice, suggesting potential activity on CB1Rs. LA - English DB - MTMT ER - TY - JOUR AU - Hus-Citharel, Annette AU - Bouby, Nadine AU - Corbani, Maithe AU - Mion, Julie AU - Mendre, Christiane AU - Darusi, Judit AU - Tömböly, Csaba AU - Trueba, Miguel AU - Serradeil-Le, Gal Claudine AU - Llorens-Cortes, Catherine AU - Guillon, Gilles TI - Characterization of a functional V-1B vasopressin receptor in the male rat kidne evidence for cross talk between V-1B and V-2 receptor signaling pathways JF - AMERICAN JOURNAL OF PHYSIOLOGY: RENAL PHYSIOLOGY J2 - AM J PHYSIOL RENAL VL - 321 PY - 2021 IS - 3 SP - F305 EP - F321 PG - 17 SN - 1931-857X DO - 10.1152/ajprenal.00081.2021 UR - https://m2.mtmt.hu/api/publication/32235213 ID - 32235213 N1 - Funding Agency and Grant Number: Institut National de la Sante et de la Recherche MedicaleInstitut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche ScientifiqueCentre National de la Recherche Scientifique (CNRS); College de France; Universite de Montpellier; Universite de Paris [ANR-18-IDEX-0001]; National Research Development and Innovation OfficeNational Research, Development & Innovation Office (NRDIO) - Hungary [K124952] Funding text: This work was supported by Institut National de la Sante et de la Recherche Medicale, Centre National de la Recherche Scientifique, College de France, Universite de Montpellier, Universite de Paris ANR-18-IDEX-0001, and National Research Development and Innovation Office K124952. AB - Although vasopressin V-1B receptor (V1BR) mRNA has been detected in the kidney, the precise renal localization as well as pharmacological and physiological properties of this receptor remain unknown. Using the selective V-1B agonist d[Leu(4), Lys(8)]VP, either fluorescent or radioactive, we showed that V1BR is mainly present in principal cells of the inner medullary collecting duct (IMCD) in the male rat kidney. Protein and mRNA expression of V1BR were very low compared with the V-2 receptor (V2R). On the microdissected IMCD, d[Leu(4), Lys(8)]VP had no effect on cAMP production but induced a dose-dependent and saturable intracellular Ca2+ concentration increase mobilization with an EC50 value in the nanomolar range. This effect involved both intracellular Ca2+ mobilization and extracellular Ca2+ influx. The selective V-1B antagonist SSR149415 strongly reduced the ability of vasopressin to increase intracellular Ca2+ concentration but also cAMP, suggesting a cooperation between V1BR and V2R in IMCD cells expressing both receptors. This cooperation arises from a cross talk between second messenger cascade involving PKC rather than receptor heterodimerization, as supported by potentiation of arginine vasopressin-stimulated cAMP production in human embryonic kidney-293 cells coexpressing the two receptor isoforms and negative results obtained by bioluminescence resonance energy transfer experiments. In vivo, only acute administration of high doses of V-1B agonist triggered significant diuretic effects, in contrast with injection of selective V-2 agonist. This study brings new data on the localization and signaling pathways of V1BR in the kidney, highlights a cross talk between V1BR and V2R in the IMCD, and suggests that V1BR may counterbalance in some pathophysiological conditions the antidiuretic effect triggered by V2R activation. NEW & NOTEWORTHY Although V1BR mRNA has been detected in the kidney, the precise renal localization as well as pharmacological and physiological properties of this receptor remain unknown. Using original pharmaceutical tools, this study brings new data on the localization and signaling pathways of V1BR, highlights a cross talk between V1BR and V-2 receptor (V2R) in the inner medullary collecting duct, and suggests that V1BR may counterbalance in some pathophysiological conditions the antidiuretic effect triggered by V2R activation. LA - English DB - MTMT ER - TY - JOUR AU - Laczkó-Rigó, Réka AU - Bakos, Éva AU - Jójárt, Rebeka AU - Tömböly, Csaba AU - Mernyák, Erzsébet AU - Laczka, Csilla TI - Selective antiproliferative effect of C-2 halogenated 13α-estrones on cells expressing Organic anion-transporting polypeptide 2B1 (OATP2B1) JF - TOXICOLOGY AND APPLIED PHARMACOLOGY J2 - TOXICOL APPL PHARM VL - 429 PY - 2021 PG - 9 SN - 0041-008X DO - 10.1016/j.taap.2021.115704 UR - https://m2.mtmt.hu/api/publication/32178981 ID - 32178981 AB - Organic anion-transporting polypeptide 2B1 (OATP2B1) is a multispecific transporter mediating the cellular uptake of steroids and numerous drugs. OATP2B1 is abundantly expressed in the intestine and is also present in various tumors. Increased steroid hormone uptake by OATP2B1 has been suggested to promote progression of hormone dependent tumors. 13 alpha-estrones are effective inhibitors of endogenous estrogen formation and are potential candidates to inhibit proliferation of hormone dependent cancers. Recently, we have identified a variety of 13 alpha/beta-estrone-based inhibitors of OATP2B1. However, the nature of this interaction, whether these inhibitors are potential transported substrates of OATP2B1 and hence may be enriched in OATP2B1overexpressing cells, has not yet been investigated. In the current study we explored the antiproliferative effect of the most effective OATP2B1 inhibitor 13 alpha/beta-estrones in control and OATP2B1-overexpressing A431 carcinoma cells. We found an increased antiproliferative effect of 3-O-benzyl 13 alpha/beta-estrones in both mock transfected and OATP2B1-overexpressing cells. However, C-2 halogenated 13 alpha-estrones had a selective OATP2B1-mediated cell growth inhibitory effect. In order to demonstrate that increased sensitization can be attributed to OATP2B1-mediated cellular uptake, tritium labeled 2-bromo-13 alpha-estrone was synthesized for direct transport measurements. These experiments revealed increased accumulation of [H-3]2-bromo-13 alpha-estrone due to OATP2B1 function. Our results indicate that C-2 halogenated 13 alpha-estrones are good candidates in the design of anti-cancer drugs targeting OATP2B1. LA - English DB - MTMT ER - TY - JOUR AU - Almási, Nikoletta AU - Murlasits, Zsolt AU - Al-Awar, Amin AU - Csonka, Ákos AU - Dvorácskó, Szabolcs AU - Tömböly, Csaba AU - Török, Szilvia AU - Bester, D. AU - Pósa, Anikó AU - Varga, Csaba AU - Kupai, Krisztina TI - Effects of aging on proteasomal-ubiquitin system, oxidative stress balance and calcium homeostasis in middle-aged female rat colon JF - PHYSIOLOGY INTERNATIONAL J2 - PHYSIOL INT VL - 108 PY - 2021 IS - 1 SP - 27 EP - 42 PG - 16 SN - 2498-602X DO - 10.1556/2060.2021.00012 UR - https://m2.mtmt.hu/api/publication/32128211 ID - 32128211 N1 - Funding Agency and Grant Number: Ministry of Human Capacities, Hungarian grant [GINOP2.3.215201600030]; [203913/2018/FEKUSTRAT] Funding text: This research was supported by GINOP2.3.215201600030 and Ministry of Human Capacities, Hungarian grant 203913/2018/FEKUSTRAT. LA - English DB - MTMT ER - TY - JOUR AU - Dvorácskó, Szabolcs AU - Lázár, László AU - Fülöp, Ferenc AU - Palkó, Márta AU - Zalán, Zita AU - Penke, Botond AU - Fülöp, Lívia AU - Tömböly, Csaba AU - Bogár, Ferenc TI - Novel High Affinity Sigma-1 Receptor Ligands from Minimal Ensemble Docking-Based Virtual Screening JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 22 PY - 2021 IS - 15 PG - 17 SN - 1661-6596 DO - 10.3390/ijms22158112 UR - https://m2.mtmt.hu/api/publication/32123857 ID - 32123857 LA - English DB - MTMT ER - TY - JOUR AU - Zádor, Ferenc AU - Joca, Sâmia AU - Nagy-Grócz, Gábor AU - Dvorácskó, Szabolcs AU - Szűcs, Edina AU - Tömböly, Csaba AU - Benyhe, Sándor AU - Vécsei, László TI - Pro-Inflammatory Cytokines: Potential Links between the Endocannabinoid System and the Kynurenine Pathway in Depression JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 22 PY - 2021 IS - 11 PG - 19 SN - 1661-6596 DO - 10.3390/ijms22115903 UR - https://m2.mtmt.hu/api/publication/32053101 ID - 32053101 N1 - Cited By :23 Export Date: 7 March 2024 Correspondence Address: Vécsei, L.; Department of Neurology, Hungary; email: vecsei.laszlo@med.u-szeged.hu Funding details: European Commission, EC, EFOP-3.6.1-16-2016-00008, GINOP 2.3.2-15-2016-00034, TUDFO/47138-1/2019-ITM Funding details: Fundação de Amparo à Pesquisa do Estado de São Paulo, FAPESP, 17/24304-0 Funding details: Aarhus Universitets Forskningsfond Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA Funding details: Innovációs és Technológiai Minisztérium Funding text 1: Funding: G.N.-G. was supported by the ÚNKP-20-4 New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund. S.J. is supported by the Aarhus University Research Foundation (AUFF starting grant) and FAPESP (17/24304-0). This research was supported by the EU-funded Hungarian grant EFOP-3.6.1-16-2016-00008 and by the TUDFO/47138-1/2019-ITM, GINOP 2.3.2-15-2016-00034. LA - English DB - MTMT ER - TY - JOUR AU - Szabó, Írisz AU - Varga, Viktória Éva AU - Dvorácskó, Szabolcs AU - Farkas, Elek Attila AU - Körmöczi, Tímea AU - Berkecz, Róbert AU - Kecskés, Szilvia AU - Menyhárt, Ákos AU - Frank, Rita AU - Hantosi, Dóra AU - Cozzi, Nicholas V. AU - Frecska, Ede AU - Tömböly, Csaba AU - Krizbai, István Adorján AU - Bari, Ferenc AU - Farkas, Eszter TI - N,N-Dimethyltryptamine attenuates spreading depolarization and restrains neurodegeneration by sigma-1 receptor activation in the ischemic rat brain JF - NEUROPHARMACOLOGY J2 - NEUROPHARMACOLOGY VL - 192 PY - 2021 PG - 13 SN - 0028-3908 DO - 10.1016/j.neuropharm.2021.108612 UR - https://m2.mtmt.hu/api/publication/32040557 ID - 32040557 LA - English DB - MTMT ER - TY - JOUR AU - Herman, Bianka Edina AU - Gardi, János AU - Julesz, János AU - Tömböly, Csaba AU - Szánti-Pintér, Eszter AU - Fehér, Klaudia AU - Skodáné Földes, Rita AU - Szécsi, Mihály TI - Steroidal ferrocenes as potential enzyme inhibitors of the estrogen biosynthesis JF - BIOLOGIA FUTURA J2 - BIOL FUTURA VL - 71 PY - 2020 IS - 3 SP - 249 EP - 264 PG - 16 SN - 2676-8615 DO - 10.1007/s42977-020-00023-7 UR - https://m2.mtmt.hu/api/publication/31365295 ID - 31365295 LA - English DB - MTMT ER -