@article{MTMT:33211172,
	title = {A cytotoxic survey on 2-amino-1H-imidazol based synthetic marine sponge alkaloid analogues},
	url = {https://m2.mtmt.hu/api/publication/33211172},
	author = {Gémes, Nikolett and Makra, Zsófia and Neuperger, Patricia and Szabó, Enikő and Balog, József Ágoston and Flink, Lili Borbála and Kari, Beáta and Hackler, László and Puskás, László and Kanizsai, Iván and Szebeni, Gábor},
	doi = {10.1002/ddr.22006},
	journal-iso = {DRUG DEVELOP RES},
	journal = {DRUG DEVELOPMENT RESEARCH},
	volume = {83},
	unique-id = {33211172},
	issn = {0272-4391},
	abstract = {Here, we describe the synthesis and biologic activity evaluation of 20 novel synthetic marine sponge alkaloid analogues with 2-amino-1H-imidazol (2-AI) core. Cytotoxicity was tested on murine 4T1 breast cancer, A549 human lung cancer, and HL-60 human myeloid leukemia cells by the resazurin assay. A total of 18 of 20 compounds showed cytotoxic effect on the cancer cell lines with different potential. Viability of healthy human fibroblasts and peripheral blood mononuclear cells upon treatment was less hampered compared to cancer cell lines supporting tumor cell specific cytotoxicity of our compounds. The most cytotoxic compounds resulted the following IC50 values 28: 2.91 µM on HL-60 cells, and 29: 3.1 µM on 4T1 cells. The A549 cells were less sensitive to the treatments with IC50 15 µM for both 28 and 29. Flow cytometry demonstrated the apoptotic effect of the most active seven compounds inducing phosphatidylserine exposure and sub-G1 fragmentation of nuclear DNA. Cell cycle arrest was also observed. Four compounds caused depolarization of the mitochondrial membrane potential as an early event of apoptosis. Two lead compounds inhibited tumor growth in vivo in the 4T1 triple negative breast cancer and A549 human lung adenocarcinoma xenograft models. Novel marine sponge alkaloid analogues are demonstrated as potential anticancer agents for further development.},
	keywords = {Mannich; 2-amino-(1H)-imidazole; 4T1 breast cancer; A549 lung cancer; HL-60 myeloid leukemia},
	year = {2022},
	eissn = {1098-2299},
	pages = {1906-1922},
	orcid-numbers = {Szebeni, Gábor/0000-0002-6998-5632}
}

@article{MTMT:32743393,
	title = {Phosphine(III)‐Triggered One‐Pot Domino Sequences towards 5,6‐Dihydropyridine‐2‐(1 H )‐One and Pyridine‐2(1 H )‐One Scaffolds},
	url = {https://m2.mtmt.hu/api/publication/32743393},
	author = {Makra, Zsófia and Madácsi, Ramóna and Martinek, Tamás and Bényei, Attila Csaba and Puskás, László and Gyuris, Márió and Kanizsai, Iván},
	doi = {10.1002/adsc.202101370},
	journal-iso = {ADV SYNTH CATAL},
	journal = {ADVANCED SYNTHESIS & CATALYSIS},
	volume = {364},
	unique-id = {32743393},
	issn = {1615-4150},
	year = {2022},
	eissn = {1615-4169},
	pages = {1134-1143},
	orcid-numbers = {Martinek, Tamás/0000-0003-3168-8066}
}

@article{MTMT:31691879,
	title = {One-Pot Access towards 4,5-Disubstituted 2-Amino-1H-imidazoles Starting from Mannich Substrates and their Transformation Utilities},
	url = {https://m2.mtmt.hu/api/publication/31691879},
	author = {Makra, Zsófia and Bényei, Attila Csaba and Puskas, Laszlo G. and Kanizsai, Iván},
	doi = {10.1002/ejoc.202001253},
	journal-iso = {EUR J ORG CHEM},
	journal = {EUROPEAN JOURNAL OF ORGANIC CHEMISTRY},
	volume = {2020},
	unique-id = {31691879},
	issn = {1434-193X},
	abstract = {An efficient protocol for the preparation of 4,5-functionalised 2-amino-1H-imidazoles as fragment-like structures was developed in isolated yields up to 95 %. The demonstrated one-pot manner includes an intramolecular oxidative annulation and ring cleavage sequence starting from Mannich precursors. The suggested one-pot sequential synthetic methodology is easy to apply in automatic and robotic chemistry laboratories for which a rapidly increasing demand is foreseen because of the ongoing revolution in the field of continuous manufacturing of pharmaceutical drug substances and products. Further transformation utilities such as Groebke-Blackburn-Bienayme 3CR and the formation of marine alkaloid analogs were also represented.},
	keywords = {MULTICOMPONENT REACTIONS; nitrogen heterocycles; Ring cleavage; reaction; Groebke–; Blackburn–; Bienaymé; One‐; pot reactions},
	year = {2020},
	eissn = {1099-0690},
	pages = {7184-7196}
}

@article{MTMT:31569407,
	title = {Synthesis and biological evaluation of 4,5,6,7-tetrahydrothieno[2,3-c]pyridine-based beta-aminonitriles and their derivatives: beta-amino carboxamides, (thio)ureas, and tetracycles},
	url = {https://m2.mtmt.hu/api/publication/31569407},
	author = {Madácsi, Ramóna and Traj, Peter and Hackler, Laszlo Jr. and Nagy, Lajos I. and Kari, Beata and Puskas, Laszlo G. and Kanizsai, Iván},
	doi = {10.1002/jhet.3800},
	journal-iso = {J HETEROCYCLIC CHEM},
	journal = {JOURNAL OF HETEROCYCLIC CHEMISTRY},
	volume = {57},
	unique-id = {31569407},
	issn = {0022-152X},
	abstract = {The preparation and cytotoxic characterization of 4,5,6,7-tetrahydrothieno[2,3-c]pyridine-based beta-aminonitriles, beta-amino carboxamides, and their (thio)urea and annulated derivatives were accomplished. Following a synthetic route involving Gewald three-component reactions (G-3CR) and a Lewis acid-catalyzed iso (thio)cyanate coupling, 30 compounds were prepared for antitumor evaluation. For derivatizations, a catalytic amount of CuOAc2 (20 mol%) was essential for improving the reactivity of either the C-2 amino function of thiophene or isocyanates. The synthesized analogues demonstrated a weak to moderate antitumor activity in a low micromolar range against A549 and K562 cancer cell lines.},
	year = {2020},
	eissn = {1943-5193},
	pages = {635-652}
}

@article{MTMT:31499509,
	title = {Acid-Catalyzed 1,3-Dipolar Cycloaddition of 2H-Azirines with Nitrones: An Unexpected Access to 1,2,4,5-Tetrasubstituted Imidazoles},
	url = {https://m2.mtmt.hu/api/publication/31499509},
	author = {Angyal, Anikó and Demjen, Andras and Wölfling, János and Puskas, Laszlo G. and Kanizsai, Iván},
	doi = {10.1021/acs.joc.9b03288},
	journal-iso = {J ORG CHEM},
	journal = {JOURNAL OF ORGANIC CHEMISTRY},
	volume = {85},
	unique-id = {31499509},
	issn = {0022-3263},
	abstract = {The first 1,3-dipolar cycloaddition of 2H-azirines with nitrones, a straightforward approach toward the regioselective synthesis of 1,2,4,5-tetrasubstituted imidazoles, is reported. This trifluoroacetic acid-catalyzed protocol tolerates a broad range of aliphatic and aromatic substrates, offering an efficient access to highly diverse, multisubstituted imidazoles in isolated yields up to 83% under mild conditions.},
	year = {2020},
	eissn = {1520-6904},
	pages = {3587-3595},
	orcid-numbers = {Wölfling, János/0000-0002-3037-309X}
}

@article{MTMT:31385279,
	title = {Imidazo[1,2-b]pyrazole-7-Carboxamide Derivative Induces Differentiation-Coupled Apoptosis of Immature Myeloid Cells Such as Acute Myeloid Leukemia and Myeloid-Derived Suppressor Cells},
	url = {https://m2.mtmt.hu/api/publication/31385279},
	author = {Kotogány, Edit and Balog, József Ágoston and Nagy, Lajos I. and Alföldi, Róbert and Bertagnolo, Valeria and Brugnoli, Federica and Demjén, András and Kovács, Anita Kármen and Batár, Péter and Mezei, Gabriella and Szabó, Renáta and Kanizsai, Iván and Varga, Csaba and Puskás, László and Szebeni, Gábor},
	doi = {10.3390/ijms21145135},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {21},
	unique-id = {31385279},
	issn = {1661-6596},
	year = {2020},
	eissn = {1422-0067},
	orcid-numbers = {Kovács, Anita Kármen/0000-0001-9805-1647; Varga, Csaba/0000-0002-2678-665X; Szebeni, Gábor/0000-0002-6998-5632}
}

@article{MTMT:31147855,
	title = {Enantioselective Synthesis of 8-Hydroxyquinoline Derivative, Q134 as a Hypoxic Adaptation Inducing Agent.},
	url = {https://m2.mtmt.hu/api/publication/31147855},
	author = {Hackler, László and Gyuris, Márió and Huzián, Orsolya and Alföldi, Róbert and Szebeni, Gábor and Madácsi, Ramóna and Knapp, Levente and Kanizsai, Iván and Puskás, László},
	doi = {10.3390/molecules24234269},
	journal-iso = {MOLECULES},
	journal = {MOLECULES},
	volume = {24},
	unique-id = {31147855},
	issn = {1420-3049},
	abstract = {Hypoxia is a common feature of neurodegenerative diseases, including Alzheimer's disease that may be responsible for disease pathogenesis and progression. Therefore, the hypoxia-inducible factor (HIF)1 system, responsible for hypoxic adaptation, is a potential therapeutic target to combat these diseases by activators of cytoprotective protein induction. We have selected a candidate molecule from our cytoprotective hydroxyquinoline library and developed a novel enantioselective synthesis for the production of its enantiomers. The use of quinidine or quinine as a catalyst enabled the preparation of enantiomer-pure products. We have utilized in vitro assays to evaluate cytoprotective activity, a fluorescence-activated cell sorting (FACS) based assay measuring mitochondrial membrane potential changes, and gene and protein expression analysis. Our data showed that the enantiomers of Q134 showed potent and similar activity in all tested assays. We have concluded that the enantiomers exert their cytoprotective activity via the HIF1 system through HIF1A protein stabilization.},
	keywords = {CYTOPROTECTION; neurodegeneration; Alzheimer's disease; enantioselective synthesis; mitochondrial membrane potential; 8-Hydroxyquinoline; HIF1A; Betti reaction},
	year = {2019},
	eissn = {1420-3049},
	orcid-numbers = {Szebeni, Gábor/0000-0002-6998-5632}
}

@article{MTMT:30644621,
	title = {The Anti-Inflammatory Role of Mannich Curcuminoids; Special Focus on Colitis},
	url = {https://m2.mtmt.hu/api/publication/30644621},
	author = {Szebeni, Gábor and Nagy, Lajos I. and Magyariné, Berkó Anikó and Nagyné Hoffmann, Alexandra and Fehér, Liliána Z. and Bagyánszki, Mária and Kari, Beáta and Balog, József Ágoston and Hackler, László and Kanizsai, Iván and Pósa, Anikó and Varga, Csaba and Puskás, László},
	doi = {10.3390/molecules24081546},
	journal-iso = {MOLECULES},
	journal = {MOLECULES},
	volume = {24},
	unique-id = {30644621},
	issn = {1420-3049},
	abstract = {The incidence of inflammatory bowel disease (IBD) increases gradually in Western countries with high need for novel therapeutic interventions. Mannich curcuminoids, C142 or C150 synthetized in our laboratory, have been tested for anti-inflammatory activity in a rat model of TNBS (2,4,6-trinitrobenzenesulphonic acid) induced colitis. Treatment with C142 or C150 reduced leukocyte infiltration to the submucosa and muscular propria of the inflamed gut. C142 or C150 rescued the loss of body weight and C150 decreased the weight of standard colon preparations proportional with 20% less tissue oedema. Both C142 and C150 curcumin analogues caused 25% decrease in the severity of colonic inflammation and haemorrhagic lesion size. Colonic MPO (myeloperoxidase) enzyme activity as an indicator of intense neutrophil infiltration was 50% decreased either by C142 or C150 Mannich curcuminoids. Lipopolysaccharide (LPS) co-treatment with Mannich curcuminoids inhibited NF-B (nuclear factor kappa B) activity on a concentration-dependent manner in an NF-B-driven luciferase expressing reporter cell line. Co-treatment with LPS and curcuminoids, C142 or C150, resulted in NF-B inhibition with 3.57 M or 1.6 M half maximal effective concentration (EC50) values, respectively. C150 exerted a profound inhibition of the expression of inflammatory cytokines, tumor necrosis factor- (TNF-), interleukin-6 (IL-6), and interleukin-4 (IL-4) in human PBMCs (peripheral blood mononuclear cells) upon LPS stimulus. Mannich curcuminoids reported herein possess a powerful anti-inflammatory activity.},
	year = {2019},
	eissn = {1420-3049},
	orcid-numbers = {Szebeni, Gábor/0000-0002-6998-5632; Magyariné, Berkó Anikó/0000-0002-1237-5745; Bagyánszki, Mária/0000-0003-3533-9461; Pósa, Anikó/0000-0003-2167-2888; Varga, Csaba/0000-0002-2678-665X}
}

@article{MTMT:30641393,
	title = {1,3-Dipolar Cycloaddition of Isatin-Derived Azomethine Ylides with 2H-Azirines: Stereoselective Synthesis of 1,3-Diazaspiro[bicyclo[3.1.0]hexane]oxindoles},
	url = {https://m2.mtmt.hu/api/publication/30641393},
	author = {Angyal, Anikó and András, Demjén and Harmat, Veronika and Wölfling, János and László, G. Puskás and Kanizsai, Iván},
	doi = {10.1021/acs.joc.9b00242},
	journal-iso = {J ORG CHEM},
	journal = {JOURNAL OF ORGANIC CHEMISTRY},
	volume = {84},
	unique-id = {30641393},
	issn = {0022-3263},
	year = {2019},
	eissn = {1520-6904},
	pages = {4273-4281},
	orcid-numbers = {Harmat, Veronika/0000-0002-1866-9904; Wölfling, János/0000-0002-3037-309X}
}

@article{MTMT:30319060,
	title = {Imidazo[1,2-b]pyrazole-7-carboxamides Induce Apoptosis in Human Leukemia Cells at Nanomolar Concentrations.},
	url = {https://m2.mtmt.hu/api/publication/30319060},
	author = {Szebeni, Gábor and Balog, József Ágoston and Demjén, András and Alföldi, Róbert and Végi, Vanessza L and Fehér, Z. Liliána and Mán, Imola and Kotogány, Edit and Gubán, Barbara and Batár, Péter and Hackler, László and Kanizsai, Iván and Puskás, László},
	doi = {10.3390/molecules23112845},
	journal-iso = {MOLECULES},
	journal = {MOLECULES},
	volume = {23},
	unique-id = {30319060},
	issn = {1420-3049},
	abstract = {Leukemia, the malignancy of the hematopoietic system accounts for 10% of cancer cases with poor overall survival rate in adults; therefore, there is a high unmet medical need for the development of novel therapeutics. Eight imidazo[1,2-b]pyrazole-7-carboxamides have been tested for cytotoxic activity against five leukemia cell lines: Acute promyelocytic leukemia (HL-60), acute monocytic leukemia (THP-1), acute T-lymphoblastic leukemia (MOLT-4), biphenotypic B myelomonocytic leukemia (MV-4-11), and erythroleukemia (K-562) cells in vitro. Imidazo[1,2-b]pyrazole-7-carboxamides hampered the viability of all five leukemia cell lines with different potential. Optimization through structure activity relationship resulted in the following IC50 values for the most effective lead compound DU385: 16.54 nM, 27.24 nM, and 32.25 nM on HL-60, MOLT-4, MV-4-11 cells, respectively. Human primary fibroblasts were much less sensitive in the applied concentration range. Both monolayer or spheroid cultures of murine 4T1 and human MCF7 breast cancer cells were less sensitive to treatment with 1.5⁻10.8 μM IC50 values. Flow cytometry confirmed the absence of necrosis and revealed 60% late apoptotic population for MV-4-11, and 50% early apoptotic population for HL-60. MOLT-4 cells showed only about 30% of total apoptotic population. Toxicogenomic study of DU385 on the most sensitive MV-4-11 cells revealed altered expression of sixteen genes as early (6 h), midterm (12 h), and late response (24 h) genes upon treatment. Changes in ALOX5AP, TXN, and SOD1 expression suggested that DU385 causes oxidative stress, which was confirmed by depletion of cellular glutathione and mitochondrial membrane depolarization induction. Imidazo[1,2-b]pyrazole-7-carboxamides reported herein induced apoptosis in human leukemia cells at nanomolar concentrations.},
	keywords = {APOPTOSIS; IMIDAZOLE; Acute myeloid leukemia; Toxicogenomics; pyrazole},
	year = {2018},
	eissn = {1420-3049},
	orcid-numbers = {Szebeni, Gábor/0000-0002-6998-5632}
}