@article{MTMT:34081319,
	title = {In vitro and in vivo antiplasmodial evaluation of sugar-modified nucleoside analogues},
	url = {https://m2.mtmt.hu/api/publication/34081319},
	author = {Bege, Miklós and Singh, Vigyasa and Sharma, Neha and Debreczeni, Nóra and Bakai-Bereczki, Ilona and Nam, Poo and Herczegh, Pál and Rathi, Brijesh and Singh, Shailja and Borbás, Anikó},
	doi = {10.1038/s41598-023-39541-4},
	journal-iso = {SCI REP},
	journal = {SCIENTIFIC REPORTS},
	volume = {13},
	unique-id = {34081319},
	issn = {2045-2322},
	abstract = {Drug-resistant Plasmodium falciparum ( Pf ) infections are a major burden on the population and the healthcare system. The establishment of Pf resistance to most existing antimalarial therapies has complicated the problem, and the emergence of resistance to artemisinin derivatives is even more concerning. It is increasingly difficult to cure malaria patients due to the limited availability of effective antimalarial drugs, resulting in an urgent need for more efficacious and affordable treatments to eradicate this disease. Herein, new nucleoside analogues including morpholino-nucleoside hybrids and thio-substituted nucleoside derivatives were prepared and evaluated for in vitro and in vivo antiparasitic activity that led a few hits especially nucleoside-thiopyranoside conjugates, which are highly effective against Pf 3D7 and Pf RKL-9 strains in submicromolar concentration. One adenosine derivative and four pyrimidine nucleoside analogues significantly reduced the parasite burden in mouse models infected with Plasmodium berghei ANKA. Importantly, no significant hemolysis and cytotoxicity towards human cell line (RAW) was observed for the hits, suggesting their safety profile. Preliminary research suggested that these thiosugar-nucleoside conjugates could be used to accelerate the antimalarial drug development pipeline and thus deserve further investigation.},
	year = {2023},
	eissn = {2045-2322},
	orcid-numbers = {Bakai-Bereczki, Ilona/0000-0003-4601-7257; Borbás, Anikó/0000-0001-8462-4547}
}

@article{MTMT:33802561,
	title = {Allosteric regulation and crystallographic fragment screening of SARS-CoV-2 NSP15 endoribonuclease},
	url = {https://m2.mtmt.hu/api/publication/33802561},
	author = {Godoy, Andre Schutzer and Nakamura, Aline Minalli and Douangamath, Alice and Song, Yun and Noske, Gabriela Dias and Gawriljuk, Victor Oliveira and Fernandes, Rafaela Sachetto and Pereira, Humberto D Muniz and Oliveira, Ketllyn Irene Zagato and Fearon, Daren and Dias, Alexandre and Krojer, Tobias and Fairhead, Michael and Powell, Alisa and Dunnet, Louise and Brandao-Neto, Jose and Skyner, Rachael and Chalk, Rod and Bajusz, Dávid and Bege, Miklós and Borbás, Anikó and Keserű, György Miklós and von Delft, Frank and Oliva, Glaucius},
	doi = {10.1093/nar/gkad314},
	journal-iso = {NUCLEIC ACIDS RES},
	journal = {NUCLEIC ACIDS RESEARCH},
	volume = {51},
	unique-id = {33802561},
	issn = {0305-1048},
	abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). The NSP15 endoribonuclease enzyme, known as NendoU, is highly conserved and plays a critical role in the ability of the virus to evade the immune system. NendoU is a promising target for the development of new antiviral drugs. However, the complexity of the enzyme's structure and kinetics, along with the broad range of recognition sequences and lack of structural complexes, hampers the development of inhibitors. Here, we performed enzymatic characterization of NendoU in its monomeric and hexameric form, showing that hexamers are allosteric enzymes with a positive cooperative index, and with no influence of manganese on enzymatic activity. Through combining cryo-electron microscopy at different pHs, X-ray crystallography and biochemical and structural analysis, we showed that NendoU can shift between open and closed forms, which probably correspond to active and inactive states, respectively. We also explored the possibility of NendoU assembling into larger supramolecular structures and proposed a mechanism for allosteric regulation. In addition, we conducted a large fragment screening campaign against NendoU and identified several new allosteric sites that could be targeted for the development of new inhibitors. Overall, our findings provide insights into the complex structure and function of NendoU and offer new opportunities for the development of inhibitors.},
	year = {2023},
	eissn = {1362-4962},
	pages = {5255-5270},
	orcid-numbers = {Godoy, Andre Schutzer/0000-0002-0613-9164; Bajusz, Dávid/0000-0003-4277-9481; Borbás, Anikó/0000-0001-8462-4547; von Delft, Frank/0000-0003-0378-0017}
}

@article{MTMT:33657380,
	title = {Triaza-tricyclanos – synthesis of a new class of tricyclic nucleoside analogues by stereoselective cascade cyclocondensation},
	url = {https://m2.mtmt.hu/api/publication/33657380},
	author = {Bege, Miklós and Herczeg, Mihály and Bakai-Bereczki, Ilona and Debreczeni, Nóra and Bényei, Attila Csaba and Herczegh, Pál and Borbás, Anikó},
	doi = {10.1039/D3OB00154G},
	journal-iso = {ORG BIOMOL CHEM},
	journal = {ORGANIC & BIOMOLECULAR CHEMISTRY},
	volume = {21},
	unique-id = {33657380},
	issn = {1477-0520},
	abstract = {Conformationally constrained tricyclic morpholino-nucleosides containing three new chirality centers were prepared with full stereoselectivity, through two consecutive hemiaminal-imidazolidine cascade reactions.},
	year = {2023},
	eissn = {1477-0539},
	pages = {2213-2219},
	orcid-numbers = {Herczeg, Mihály/0000-0002-7938-9789; Bakai-Bereczki, Ilona/0000-0003-4601-7257; Borbás, Anikó/0000-0001-8462-4547}
}

@article{MTMT:33297309,
	title = {N‐Fluoroalkylated Morpholinos – a New Class of Nucleoside Analogues},
	url = {https://m2.mtmt.hu/api/publication/33297309},
	author = {Debreczeni, Nóra and Hotzi, Judit and Bege, Miklós and Lovas, Miklós and Mező, Erika and Bakai-Bereczki, Ilona and Herczegh, Pál and Kiss, Loránd and Borbás, Anikó},
	doi = {10.1002/chem.202203248},
	journal-iso = {CHEM-EUR J},
	journal = {CHEMISTRY-A EUROPEAN JOURNAL},
	volume = {29},
	unique-id = {33297309},
	issn = {0947-6539},
	year = {2023},
	eissn = {1521-3765},
	orcid-numbers = {Mező, Erika/0000-0002-8329-6745; Bakai-Bereczki, Ilona/0000-0003-4601-7257; Herczegh, Pál/0000-0003-4265-5518; Kiss, Loránd/0000-0003-2346-9816; Borbás, Anikó/0000-0001-8462-4547}
}

@article{MTMT:33663027,
	title = {Nukleozidanalóg hatóanyagok használata a Covid-19 kezelésére},
	url = {https://m2.mtmt.hu/api/publication/33663027},
	author = {Bege, Miklós},
	journal-iso = {GYÓGYSZERÉSZET},
	journal = {GYÓGYSZERÉSZET},
	volume = {66},
	unique-id = {33663027},
	issn = {0017-6036},
	year = {2022},
	pages = {232-235}
}

@article{MTMT:33663026,
	title = {Géncsendesítő gyógyszerek I. - Bevezetés a természetes és mesterséges nukleinsavak világába},
	url = {https://m2.mtmt.hu/api/publication/33663026},
	author = {Bege, Miklós},
	journal-iso = {GYÓGYSZERÉSZET},
	journal = {GYÓGYSZERÉSZET},
	volume = {66},
	unique-id = {33663026},
	issn = {0017-6036},
	year = {2022},
	pages = {395-400}
}

@article{MTMT:33170957,
	title = {Géncsendesítő Gyógyszerek II: - Transzlációgátló antiszenz oligonukleotidok},
	url = {https://m2.mtmt.hu/api/publication/33170957},
	author = {Bege, Miklós},
	journal-iso = {GYÓGYSZERÉSZET},
	journal = {GYÓGYSZERÉSZET},
	volume = {16},
	unique-id = {33170957},
	issn = {0017-6036},
	year = {2022},
	pages = {451-453}
}

@article{MTMT:33170331,
	title = {Synthesis and Anticancer and Antiviral Activities of C-2′-Branched Arabinonucleosides},
	url = {https://m2.mtmt.hu/api/publication/33170331},
	author = {Bege, Miklós and Kiss, Alexandra and Bakai-Bereczki, Ilona and Hodek, Jan and Polyák, Lenke and Szemán-Nagy, Gábor and Naesens, Lieve and Weber, Jan and Borbás, Anikó},
	doi = {10.3390/ijms232012566},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {23},
	unique-id = {33170331},
	issn = {1661-6596},
	abstract = {d-Arabinofuranosyl-pyrimidine and -purine nucleoside analogues containing alkylthio-, acetylthio- or 1-thiosugar substituents at the C2’ position were prepared from the corresponding 3’,5’-O-silylene acetal-protected nucleoside 2’-exomethylenes by photoinitiated, radical-mediated hydrothiolation reactions. Although the stereochemical outcome of the hydrothiolation depended on the structure of both the thiol and the furanoside aglycone, in general, high d-arabino selectivity was obtained. The cytotoxic effect of the arabinonucleosides was studied on tumorous SCC (mouse squamous cell) and immortalized control HaCaT (human keratinocyte) cell lines by MTT assay. Three pyrimidine nucleosides containing C2’-butylsulfanylmethyl or -acetylthiomethyl groups showed promising cytotoxicity at low micromolar concentrations with good selectivity towards tumor cells. SAR analysis using a methyl β-d-arabinofuranoside reference compound showed that the silyl-protecting group, the nucleobase and the corresponding C2’ substituent are crucial for the cell growth inhibitory activity. The effects of the three most active nucleoside analogues on parameters indicative of cytotoxicity, such as cell size, division time and cell generation time, were investigated by near-infrared live cell imaging, which showed that the 2’-acetylthiomethyluridine derivative induced the most significant functional and morphological changes. Some nucleoside analogues also exerted anti-SARS-CoV-2 and/or anti-HCoV-229E activity with low micromolar EC50 values; however, the antiviral activity was always accompanied by significant cytotoxicity.},
	keywords = {Antiviral; CORONAVIRUS; time-lapse imaging; Anti-tumor; Nucleoside analogue; SARS-CoV-2; photocatalytic thiol-ene reaction},
	year = {2022},
	eissn = {1422-0067},
	orcid-numbers = {Bakai-Bereczki, Ilona/0000-0003-4601-7257; Szemán-Nagy, Gábor/0000-0003-1906-0188; Naesens, Lieve/0000-0001-9742-9302; Borbás, Anikó/0000-0001-8462-4547}
}

@article{MTMT:33037647,
	title = {Egy újonnan szintetizált adenozin analóg, a hipoxantin-triciklánó hatása izolált patkány bal és jobb pitvaron},
	url = {https://m2.mtmt.hu/api/publication/33037647},
	author = {Óvári, Ignác and Szilágyi, Viktória and Viczján, Gábor and Lampé, Nóra and Bege, Miklós and Borbás, Anikó and Herczeg, Pál and Juhász, Béla and Gesztelyi, Rudolf and Erdei, Tamás Dániel},
	doi = {10.56626/egis.v1i1.7059},
	journal-iso = {EÜ INNOV SZLE},
	journal = {EGÉSZSÉGÜGYI INNOVÁCIÓS SZEMLE},
	volume = {1},
	unique-id = {33037647},
	abstract = {A hipoxantin-triciklánó egy a DE GYTK Gyógyszerészi Kémia Tanszéken szintetizált adenozin analóg, melyben az adenint hipoxantin, a ribózt pedig egy kondenzált triciklikus molekularész helyettesíti. Munkánk során a hipoxantin-triciklánó hatását vizsgáltuk a pitvari myocardium A1 adenozinerg rendszerére, melynek (pozitív agonista általi) aktivációja számos protektív folyamatért, köztük negatív trop hatásokért felelős.
		
		A vizsgálatokat hím Wistar patkányokból izolált bal pitvari fülcsén és teljes jobb pitvaron végeztük. A preparátumokat 95% O2 és 5% CO2 gázeleggyel szellőztetett, 36°C-os Krebs oldatot tartalmazó szervkádakban függesztettük fel 10 mN alapfeszülés mellett. A bal pitvarokat állandó frekvencián ingereltük (3 Hz; 1 ms; 1-1,5 V), míg a jobb pitvarok spontán húzódtak össze. A preparátumokon az adenozin és a hipoxantin-triciklánó inotrop és chronotrop hatását vizsgáltuk külön-külön és együtt, továbbá CPX (8-cyclopentyl-1,3-dipropylxanthine; reverzibilis A1 adenozin receptor antagonista) hiányában és jelenlétében.
		
		Eredményeink alapján az adenozin mind a bal, mind a jobb pitvarokon hasonló mértékű, erőteljes negatív inotrop hatást fejtett ki. A hipoxantin-triciklánó ezzel szemben mérsékelt pozitív inotrop hatást váltott ki, ami hasonló mértékű volt a jobb és a bal pitvarokon. Az inotropia alakulásával összhangban, az adenozin markánsan negatív, míg a hipoxantin-triciklánó kismértékben pozitív chronotrop hatásúnak bizonyult a jobb pitvarokon. A CPX erősen (és szignifikánsan) gátolta az adenozin hatásait, de csak kisebb mértékű (és nem szignifikáns) gátlást hozott létre a hipoxantin-triciklánó hatásaival szemben. A hipoxantin-triciklánó hatásai teljes mértékben áttörhetőek voltak adenozinnal. Mindezek hátterében felvethető, hogy az adenozin könnyen le tudja szorítani a hipoxantin-triciklánót az A1 adenozin receptorról, de (ehelyett vagy emellett) elképzelhető, hogy a hipoxantin-triciklánó az A1 adenozin receptortól független útvonalon is hat. A hipoxantin-triciklánó tehát feltehetően a myocardialis A1 adenozin receptor reverzibilis, ortosztérikus, inverz agonistája, melynek ugyanakkor más támadáspontja is lehet a myocardiumban.
		
		The  hypoxanthine-tricyclano  is  a  new  adenosine  analogue,  in  which  adenine  and  ribose  are  replaced  by hypoxanthine and a fused tricyclic moiety, respectively, synthetized in the Department of Pharma-ceutical Chemistry (Faculty of Pharmacy, University of Debrecen). In the current study, we investigated the effect of hypoxanthine-tricyclano on the A1 adenosinergic system of the rat atrial myocardium, ac-tivation of which (by a positive agonist) is responsible for several protective actions, including negative tropic effects.The left atrial auricle and the whole right atrium were isolated from male Wistar rats and mounted at 10   mN resting tension in 10 mL vertical organ chambers containing Krebs solution (36 °C) oxygenated with 95% O2 and 5% CO2. Left atria were paced (3 Hz, 1 ms, 1-2 V), while right atria worked spontaneous-ly. The inotropic and chronotropic effects of adenosine and hypoxanthine-tricyclano were investigated (separately and in combination), in the absence and presence of CPX (8-cyclopenty l-1,3-dipropylxan-thine), a reversible A1 adenosine receptor antagonist.Adenosine elicited a strong negative inotropic effect on both the left and right atria (to a similar extent). In contrast, hypoxanthine-tricyclano produced a moderate positive inotropic effect in the left and right atria (also to a similar extent). In consistent with the inotropic effects, adenosine exerted a substantial negative chronotropic effect, and hypoxanthine-tricyclano elicited a slight positive chronotropic effect in the right atria. CPX strongly (and statistically significantly) blunted the effects of adenosine but it pro-duced only a minor (and not significant) inhibition against actions of hypoxanthine-tricyclano. In addi-tion, the effects of hypoxanthine-tricyclano were completely surmountable with adenosine. This can be explained by supposing that adenosine can easily displace hypoxanthine-tricyclano from their receptor, and, alternatively or in addition, that hypoxanthine-tricyclano may also act in a pathway independent from  the  A1  adenosine  receptor.  Thus,  hypoxanthine-tricyclano  is  probably  a  reversible,  orthosteric,  inverse  agonist  of  the  myocardial  A1  adenosine  receptor  that  might  also  have  another  target  in  the  myocardium.},
	keywords = {HEART; adenosine; inotropic; atrium; Szív; ADENOZIN; A1 adenosine receptor; Chronotropic; hypoxanthine-tricyclano; hipoxantin-triciklánó; A1 adenozin receptor; pitvar; inotrop; chronotrop},
	year = {2022},
	eissn = {2939-6026},
	pages = {9-16},
	orcid-numbers = {Borbás, Anikó/0000-0001-8462-4547; Gesztelyi, Rudolf/0000-0001-7911-055X}
}

@article{MTMT:33025875,
	title = {The Medicinal Chemistry of Artificial Nucleic Acids and Therapeutic Oligonucleotides},
	url = {https://m2.mtmt.hu/api/publication/33025875},
	author = {Bege, Miklós and Borbás, Anikó},
	doi = {10.3390/ph15080909},
	journal-iso = {PHARMACEUTICALS-BASE},
	journal = {PHARMACEUTICALS},
	volume = {15},
	unique-id = {33025875},
	abstract = {Nucleic acids play a central role in human biology, making them suitable and attractive tools for therapeutic applications. While conventional drugs generally target proteins and induce transient therapeutic effects, nucleic acid medicines can achieve long-lasting or curative effects by targeting the genetic bases of diseases. However, native oligonucleotides are characterized by low in vivo stability due to nuclease sensitivity and unfavourable physicochemical properties due to their polyanionic nature, which are obstacles to their therapeutic use. A myriad of synthetic oligonucleotides have been prepared in the last few decades and it has been shown that proper chemical modifications to either the nucleobase, the ribofuranose unit or the phosphate backbone can protect the nucleic acids from degradation, enable efficient cellular uptake and target localization ensuring the efficiency of the oligonucleotide-based therapy. In this review, we present a summary of structure and properties of artificial nucleic acids containing nucleobase, sugar or backbone modifications, and provide an overview of the structure and mechanism of action of approved oligonucleotide drugs including gene silencing agents, aptamers and mRNA vaccines.},
	year = {2022},
	eissn = {1424-8247},
	orcid-numbers = {Borbás, Anikó/0000-0001-8462-4547}
}