@article{MTMT:34789041,
	title = {Synthesis of Estrone Heterodimers and Evaluation of Their In Vitro Antiproliferative Activity},
	url = {https://m2.mtmt.hu/api/publication/34789041},
	author = {Bózsity-Faragó, Noémi and Nagy, Viktória and Szabó, Johanna and Pálházi, Balázs and Kele, Zoltán and Resch, Vivien Erzsébet and Paragi, Gábor and Zupkó, István and Minorics, Renáta and Mernyák, Erzsébet},
	doi = {10.3390/ijms25084274},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {25},
	unique-id = {34789041},
	issn = {1661-6596},
	abstract = {Directed structural modifications of natural products offer excellent opportunities to develop selectively acting drug candidates. Natural product hybrids represent a particular compound group. The components of hybrids constructed from different molecular entities may result in synergic action with diminished side effects. Steroidal homo- or heterodimers deserve special attention owing to their potentially high anticancer effect. Inspired by our recently described antiproliferative core-modified estrone derivatives, here, we combined them into heterodimers via Cu(I)-catalyzed azide–alkyne cycloaddition reactions. The two trans-16-azido-3-(O-benzyl)-17-hydroxy-13α-estrone derivatives were reacted with 3-O-propargyl-D-secoestrone alcohol or oxime. The antiproliferative activities of the four newly synthesized dimers were evaluated against a panel of human adherent gynecological cancer cell lines (cervical: Hela, SiHa, C33A; breast: MCF-7, T47D, MDA-MB-231, MDA-MB-361; ovarian: A2780). One heterodimer (12) exerted substantial antiproliferative activity against all investigated cell lines in the submicromolar or low micromolar range. A pronounced proapoptotic effect was observed by fluorescent double staining and flow cytometry on three cervical cell lines. Additionally, cell cycle blockade in the G2/M phase was detected, which might be a consequence of the effect of the dimer on tubulin polymerization. Computational calculations on the taxoid binding site of tubulin revealed potential binding of both steroidal building blocks, mainly with hydrophobic interactions and water bridges.},
	year = {2024},
	eissn = {1422-0067},
	orcid-numbers = {Resch, Vivien Erzsébet/0000-0003-0044-5731; Paragi, Gábor/0000-0001-5408-1748; Zupkó, István/0000-0003-3243-5300; Minorics, Renáta/0000-0001-9685-813X; Mernyák, Erzsébet/0000-0003-4494-1817}
}

@article{MTMT:34071100,
	title = {Diatomic molecule in a strong infrared laser field: level-shifts and bond-length change due to laser-dressed Morse potential},
	url = {https://m2.mtmt.hu/api/publication/34071100},
	author = {Varró, Sándor and Hack, Szabolcs and Paragi, Gábor and Földi, Péter and Barna, Imre Ferenc and Czirják, Attila},
	doi = {10.1088/1367-2630/acde9e},
	journal-iso = {NEW J PHYS},
	journal = {NEW JOURNAL OF PHYSICS},
	volume = {25},
	unique-id = {34071100},
	issn = {1367-2630},
	abstract = {We present a general mathematical procedure to handle interactions described by a Morse potential in the presence of a strong harmonic excitation. We account for permanent and field-induced terms and their gradients in the dipole moment function, and we derive analytic formulae for the bond-length change and for the shifted energy eigenvalues of the vibrations, by using the Kramers-Henneberger frame. We apply these results to the important cases of H-2 and LiH, driven by a near- or mid-infrared laser in the 10(13) W cm(-2) intensity range.},
	keywords = {DISSOCIATION; DENSITY; POLARIZABILITIES; Equation; Molecular vibrations; BASIS-SETS; EARLY UNIVERSE; Vibrational levels; strong-field phenomena; Lithium hydride; off-resonant excitation; Kramers-Henneberger frame},
	year = {2023},
	eissn = {1367-2630},
	orcid-numbers = {Varró, Sándor/0000-0002-7246-7369; Hack, Szabolcs/0000-0003-0313-8841; Paragi, Gábor/0000-0001-5408-1748; Földi, Péter/0000-0002-0311-3532; Barna, Imre Ferenc/0000-0001-6206-3910}
}

@article{MTMT:33727646,
	title = {Investigation of the Antineoplastic Effects of 2-(4-Chlorophenyl)-13α-Estrone Sulfamate against the HPV16-Positive Human Invasive Cervical Carcinoma Cell Line SiHa},
	url = {https://m2.mtmt.hu/api/publication/33727646},
	author = {Ali, Hazhmat and Traj, Péter and Szebeni, Gábor and Gémes, Nikolett and Resch, Vivien Erzsébet and Paragi, Gábor and Mernyák, Erzsébet and Minorics, Renáta and Zupkó, István},
	doi = {10.3390/ijms24076625},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {24},
	unique-id = {33727646},
	issn = {1661-6596},
	abstract = {Cervical carcinoma is one of the most frequent malignant gynecological cancers in women of reproductive age. Because of the poor tolerability of currently available chemotherapeutic agents, efforts have been focused on developing innovative molecules, including steroids, that exert antineoplastic effects with a better safety profile. In addition to their endocrine properties, certain estrogens exhibit additional biological activities, such as antiangiogenic and anticancer effects. Based on previous studies, the antineoplastic properties of 13α-estrone sulfamate derivatives (13AES1-3) were investigated, and the mechanism of action for the most promising compound 13AES3 was explored. Based on their effects on the viability of different human adherent gynecological cancer cells, the SiHa cervical cell line was used for mechanistic experiments. The most active analog 13AES3 was shown to exert considerable proapoptotic effects, as evidenced by a colorimetric caspase-3 assay and fluorescent double staining. It also elicited antimigratory and anti-invasive effects in a concentration-dependent manner, as evidenced by wound healing and Boyden chamber assays, respectively. Regarding their mechanism of action, 13AES derivatives were shown to inhibit tubulin polymerization, and computer simulations provided a possible explanation for the importance of the presence of the chlorophenyl ring on the estrane skeleton. 13AES3 is considered to be the first 13α-estrone derivative with a significant antineoplastic potency against SiHa cancer cells. Therefore, it might serve as a valuable lead molecule for the design of anticancer agents targeting cervical carcinomas.},
	keywords = {APOPTOSIS; Antiproliferative; anti-invasive; 13α-estrone and cervical carcinoma; tubulin-microtubule system},
	year = {2023},
	eissn = {1422-0067},
	orcid-numbers = {Szebeni, Gábor/0000-0002-6998-5632; Resch, Vivien Erzsébet/0000-0003-0044-5731; Paragi, Gábor/0000-0001-5408-1748; Mernyák, Erzsébet/0000-0003-4494-1817; Minorics, Renáta/0000-0001-9685-813X; Zupkó, István/0000-0003-3243-5300}
}

@article{MTMT:33712712,
	title = {Structural Adaptation of the Single-Stranded DNA-Binding Protein C-Terminal to DNA Metabolizing Partners Guides Inhibitor Design},
	url = {https://m2.mtmt.hu/api/publication/33712712},
	author = {Tököli, Attila and Bodnár, Brigitta and Bogár, Ferenc and Paragi, Gábor and Hetényi, Anasztázia and Bartus, Éva and Wéber, Edit and Hegedüs, Zsófia and Szabó, Zoltán and Kecskeméti, Gábor and Szakonyi, Gerda and Martinek, Tamás},
	doi = {10.3390/pharmaceutics15041032},
	journal-iso = {PHARMACEUTICS},
	journal = {PHARMACEUTICS},
	volume = {15},
	unique-id = {33712712},
	issn = {1999-4923},
	abstract = {Single-stranded DNA-binding protein (SSB) is a bacterial interaction hub and an appealing target for antimicrobial therapy. Understanding the structural adaptation of the disordered SSB C-terminus (SSB-Ct) to DNA metabolizing enzymes (e.g., ExoI and RecO) is essential for designing high-affinity SSB mimetic inhibitors. Molecular dynamics simulations revealed the transient interactions of SSB-Ct with two hot spots on ExoI and RecO. The residual flexibility of the peptide–protein complexes allows adaptive molecular recognition. Scanning with non-canonical amino acids revealed that modifications at both termini of SSB-Ct could increase the affinity, supporting the two-hot-spot binding model. Combining unnatural amino acid substitutions on both segments of the peptide resulted in enthalpy-enhanced affinity, accompanied by enthalpy–entropy compensation, as determined by isothermal calorimetry. NMR data and molecular modeling confirmed the reduced flexibility of the improved affinity complexes. Our results highlight that the SSB-Ct mimetics bind to the DNA metabolizing targets through the hot spots, interacting with both of segments of the ligands.},
	year = {2023},
	eissn = {1999-4923},
	orcid-numbers = {Tököli, Attila/0000-0001-8413-3182; Bogár, Ferenc/0000-0002-0611-1452; Paragi, Gábor/0000-0001-5408-1748; Hetényi, Anasztázia/0000-0001-8080-6992; Bartus, Éva/0000-0001-9976-6978; Wéber, Edit/0000-0002-5904-0619; Hegedüs, Zsófia/0000-0002-5546-8167; Szabó, Zoltán/0000-0001-8278-8038; Kecskeméti, Gábor/0000-0002-5584-6869; Szakonyi, Gerda/0000-0002-4366-4283; Martinek, Tamás/0000-0003-3168-8066}
}

@article{MTMT:33594496,
	title = {Synthesis and Antiproliferative Activity of Steroidal Diaryl Ethers},
	url = {https://m2.mtmt.hu/api/publication/33594496},
	author = {Kovács, Édua and Ali, Hazhmat and Minorics, Renáta and Traj, Péter and Resch, Vivien Erzsébet and Paragi, Gábor and Bruszel, Bella and Zupkó, István and Mernyák, Erzsébet},
	doi = {10.3390/molecules28031196},
	journal-iso = {MOLECULES},
	journal = {MOLECULES},
	volume = {28},
	unique-id = {33594496},
	issn = {1420-3049},
	abstract = {Novel 13α-estrone derivatives have been synthesized via direct arylation of the phenolic hydroxy function. Chan–Lam couplings of arylboronic acids with 13α-estrone as a nucleophilic partner were carried out under copper catalysis. The antiproliferative activities of the newly synthesized diaryl ethers against a panel of human cancer cell lines (A2780, MCF-7, MDA-MB 231, HeLa, SiHa) were investigated by means of MTT assays. The quinoline derivative displayed substantial antiproliferative activity against MCF-7 and HeLa cell lines with low micromolar IC50 values. Disturbance of tubulin polymerization has been confirmed by microplate-based photometric assay. Computational calculations reveal significant interactions of the quinoline derivative with the taxoid binding site of tubulin.},
	year = {2023},
	eissn = {1420-3049},
	orcid-numbers = {Minorics, Renáta/0000-0001-9685-813X; Resch, Vivien Erzsébet/0000-0003-0044-5731; Paragi, Gábor/0000-0001-5408-1748; Zupkó, István/0000-0003-3243-5300; Mernyák, Erzsébet/0000-0003-4494-1817}
}

@article{MTMT:33181371,
	title = {Quinone binding site in a type VI sulfide:quinone oxidoreductase},
	url = {https://m2.mtmt.hu/api/publication/33181371},
	author = {Miklovics, Nikolett and Duzs, Ágnes and Balogh, Fanni and Paragi, Gábor and Rákhely, Gábor and Tóth, András},
	doi = {10.1007/s00253-022-12202-8},
	journal-iso = {APPL MICROBIOL BIOT},
	journal = {APPLIED MICROBIOLOGY AND BIOTECHNOLOGY},
	volume = {106},
	unique-id = {33181371},
	issn = {0175-7598},
	abstract = {Monotopic membrane-bound flavoproteins, sulfide:quinone oxidoreductases (SQRs), have a variety of physiological functions, including sulfide detoxification. SQR enzymes are classified into six groups. SQRs use the flavin adenine dinucleotide (FAD) cofactor to transfer electrons from sulfide to quinone. A type VI SQR of the photosynthetic purple sulfur bacterium, Thiocapsa roseopersicina (TrSqrF), has been previously characterized, and the mechanism of sulfide oxidation has been proposed. This paper reports the characterization of quinone binding site (QBS) of TrSqrF composed of conserved aromatic and apolar amino acids. Val331, Ile333, and Phe366 were identified near the benzoquinone ring of enzyme-bound decylubiquinone (dUQ) using the TrSqrF homology model. In silico analysis revealed that Val331 and Ile333 alternately connected with the quinone head group via hydrogen bonds, and Phe366 and Trp369 bound the quinones via hydrophobic interactions. TrSqrF variants containing alanine (V331A, I333A, F366A) and aromatic amino acid (V331F, I333F, F366Y), as well as a C-terminal alpha-helix deletion (CTD) mutant were generated. These amino acids are critical for quinone binding and, thus, catalysis. Spectroscopic analyses proved that all mutants contained FAD. I333F replacement resulted in the lack of the charge transfer complex. In summary, the interactions described above maintain the quinone molecule's head in an optimal position for direct electron transfer from FAD. Surprisingly, the CTD mutant retained a relatively high level of specific activity while remaining membrane-anchored. This is a unique study because it focuses on the QBS and the oxidative stage of a type VI sulfide-dependent quinone reduction.},
	keywords = {Sulfur metabolism; Disulfide reductase; Quinone reduction; Sulfide: quinone oxidoreductase (SQR); Quinone binding site},
	year = {2022},
	eissn = {1432-0614},
	pages = {7505-7517},
	orcid-numbers = {Paragi, Gábor/0000-0001-5408-1748; Rákhely, Gábor/0000-0003-2557-3641}
}

@article{MTMT:32818711,
	title = {Synthesis of Heterocycles and Nucleosides Forming Higher—Order Structures},
	url = {https://m2.mtmt.hu/api/publication/32818711},
	author = {Váradi, Zoltán and Paragi, Gábor and Kupihár, Zoltán and Kele, Zoltán and Kovács, Lajos},
	doi = {10.3390/ecsoc-25-11705},
	journal-iso = {CHEM PROC},
	journal = {CHEMISTRY PROCEEDINGS},
	volume = {8},
	unique-id = {32818711},
	year = {2022},
	eissn = {2673-4583},
	orcid-numbers = {Paragi, Gábor/0000-0001-5408-1748; Kupihár, Zoltán/0000-0001-5499-7617; Kele, Zoltán/0000-0002-4401-0302; Kovács, Lajos/0000-0002-0331-3980}
}

@article{MTMT:32161034,
	title = {Microwave-assisted Phospha-Michael addition reactions in the 13alpha-oestrone series and in vitro antiproliferative properties},
	url = {https://m2.mtmt.hu/api/publication/32161034},
	author = {Mernyák, Erzsébet and Bartha, Sándor and Kóczán , Lili and Jójárt, Rebeka and Resch, Vivien Erzsébet and Paragi, Gábor and Vágvölgyi, Máté and Hunyadi, Attila and Bruszel, Bella and Zupkó, István and Minorics, Renáta},
	doi = {10.1080/14756366.2021.1963241},
	journal-iso = {J ENZYM INHIB MED CH},
	journal = {JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY},
	volume = {36},
	unique-id = {32161034},
	issn = {1475-6366},
	year = {2021},
	eissn = {1475-6374},
	pages = {1931-1937},
	orcid-numbers = {Mernyák, Erzsébet/0000-0003-4494-1817; Resch, Vivien Erzsébet/0000-0003-0044-5731; Paragi, Gábor/0000-0001-5408-1748; Vágvölgyi, Máté/0000-0002-2233-9422; Hunyadi, Attila/0000-0003-0074-3472; Zupkó, István/0000-0003-3243-5300; Minorics, Renáta/0000-0001-9685-813X}
}

@article{MTMT:32096593,
	title = {Synthesis and evaluation of AKR1C inhibitory properties of A-ring halogenated oestrone derivatives},
	url = {https://m2.mtmt.hu/api/publication/32096593},
	author = {Sinreih, Maša and Jójárt, Rebeka and Kele, Zoltán and Büdefeld, Tomaž and Paragi, Gábor and Mernyák, Erzsébet and Rižner, Tea Lanišnik},
	doi = {10.1080/14756366.2021.1937142},
	journal-iso = {J ENZYM INHIB MED CH},
	journal = {JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY},
	volume = {36},
	unique-id = {32096593},
	issn = {1475-6366},
	year = {2021},
	eissn = {1475-6374},
	pages = {1500-1508},
	orcid-numbers = {Kele, Zoltán/0000-0002-4401-0302; Paragi, Gábor/0000-0001-5408-1748; Mernyák, Erzsébet/0000-0003-4494-1817}
}

@article{MTMT:32049042,
	title = {Cooperative Self-Assembly in Linear Chains Based on Halogen Bonds},
	url = {https://m2.mtmt.hu/api/publication/32049042},
	author = {Vermeeren, Pascal and Wolters, Lando P. and Paragi, Gábor and Fonseca, Guerra Celia},
	doi = {10.1002/cplu.202100093},
	journal-iso = {CHEMPLUSCHEM},
	journal = {CHEMPLUSCHEM},
	volume = {86},
	unique-id = {32049042},
	issn = {2192-6506},
	abstract = {Cooperative properties of halogen bonds were investigated with computational experiments based on dispersion-corrected relativistic density functional theory. The bonding mechanism in linear chains of cyanogen halide (X-CN), halocyanoacetylene (X-CC-CN), and 4-halobenzonitrile (X-C6H4-CN) were examined for X = H, Cl, Br, and I. Our energy decomposition and Kohn-Sham molecular-orbital analyses revealed the bonding mechanism of the studied systems. Cyanogen halide and halocyanoacetylene chains possess an extra stabilizing effect with increasing chain size, whereas the 4-halobenzonitrile chains do not. This cooperativity can be traced back to charge separation within the sigma-electronic system by charge-transfer between the lone-pair orbital of the nitrogen (sigma(HOMO)) on one unit and the acceptor orbital of the C-X (sigma*(LUMO)) on the adjacent unit. As such, the HOMO-LUMO gap in the sigma-system decreases, and the cooperativity increases with chain length revealing the similarity in the bonding mechanisms of hydrogen and halogen bonds.},
	keywords = {COOPERATIVITY; COMPLEXES; Electrostatics; HYDROGEN-BONDS; MO theory; COVALENCY; Halogen bonding; energy decomposition analysis; activation strain model; BASE-PAIRS},
	year = {2021},
	eissn = {2192-6506},
	pages = {812-819},
	orcid-numbers = {Vermeeren, Pascal/0000-0002-2100-6837; Wolters, Lando P./0000-0003-0052-0121; Paragi, Gábor/0000-0001-5408-1748; Fonseca, Guerra Celia/0000-0002-2973-5321}
}