@article{MTMT:1365862, title = {In vitro and in vivo multidrug resistance reversal activity by a Betti-base derivative of tylosin}, url = {https://m2.mtmt.hu/api/publication/1365862}, author = {Gyemant, N and Engi, Helga and Schelz, Zsuzsanna and Szatmári, István and Toth, D and Fülöp, Ferenc and Molnár, József and de Witte, PAM}, doi = {10.1038/sj.bjc.6605716}, journal-iso = {BRIT J CANCER}, journal = {BRITISH JOURNAL OF CANCER}, volume = {103}, unique-id = {1365862}, issn = {0007-0920}, abstract = {BACKGROUND: The multidrug resistance (MDR) proteins are present in a majority of human tumours. Their activity is important to understand the chemotherapeutic failure. A search for MDR-reversing compounds was conducted among various Betti-base derivatives of tylosin. METHODS: Here, we evaluate the in vitro and in vivo P-glycoprotein (P-gp)-modulating activity of the most promising compound N-tylosil-1-a-amino-(3-bromophenyl)-methyl-2-naphthol (TBN) using human MDR1 gene-transfected and parental L5178 mouse lymphoma cell lines. RESULTS: In vitro experiments showed that TBN dramatically increased the P-gp-mediated cellular uptake of the fluorescent substrate rhodamine 123. Similarly, TBN was found to act as a very potent enhancer of the cytotoxicity of doxorubicin on the resistant cell line. We also provide in vivo evidence using DBA/2 mice in support for an increased tumoural accumulation of doxorubicin, without affecting its tissue distribution, resulting in an enhanced antitumoural effect. CONCLUSION: Our results suggest that TBN is a potent modulator of the P-gp membrane pump and that the compound could be of clinical relevance to improve the efficacy of chemotherapy in MDR cancers. British Journal of Cancer (2010) 103, 178-185. doi: 10.1038/sj.bjc.6605716 www.bjcancer.com Published online 15 June 2010 (C) 2010 Cancer Research UK}, keywords = {CELLS; BINDING; COMBINATION; RESISTANCE; CANCER; P-GLYCOPROTEIN; CARCINOMA; PACLITAXEL; doxorubicin; Anthracyclines; PHASE-I; MODULATOR; P-GLYCOPROTEIN INHIBITOR; tylosin; Betti-base; tumour}, year = {2010}, eissn = {1532-1827}, pages = {178-185}, orcid-numbers = {Schelz, Zsuzsanna/0000-0002-8519-4830; Szatmári, István/0000-0002-8571-5229; Fülöp, Ferenc/0000-0003-1066-5287} } @article{MTMT:1078937, title = {Synthesis and conformational analysis of naphth[1 ',2 ': 5,6][1,3]oxazino[3,2-c][1,3]benzoxazine and naphth[1 ',2 ': 5,6][1,3]oxazino[3,4-c][1,3]benzoxazine derivatives}, url = {https://m2.mtmt.hu/api/publication/1078937}, author = {Heydenreich, M and Koch, A and Klod, S and Szatmári, István and Fülöp, Ferenc and Kleinpeter, E}, doi = {10.1016/j.tet.2006.09.037}, journal-iso = {TETRAHEDRON}, journal = {TETRAHEDRON}, volume = {62}, unique-id = {1078937}, issn = {0040-4020}, abstract = {A new functional group, the hydroxy group, was inserted into a Betti base by reaction with salicylaldehyde, and the naphthoxazine derivatives thus obtained were converted by ring-closure reactions with formaldehyde, acetaldehyde, propionaldehyde or phosgene to the corresponding naphth[1'2:5,6][1,3]oxazino[3,2-c][1,3]benzoxazine derivatives. Further, the conformational analysis of these polycyclic compounds by NMR spectroscopy and an accompanying molecular modelling are reported; especially, both quantitative anisotropic ring current effects of the aromatic moieties in these compounds and steric substituent effects were employed to determine the stereochemistry of the naphthoxazinobenzoxazine derivatives. (c) 2006 Published by Elsevier Ltd.}, year = {2006}, eissn = {1464-5416}, pages = {11081-11089}, orcid-numbers = {Szatmári, István/0000-0002-8571-5229; Fülöp, Ferenc/0000-0003-1066-5287} } @article{MTMT:1013251, title = {Stereoelectronic effects in ring-chain tautomerism of 1,3-diarylnaphth[1,2-e][1,3]oxazines and 3-alkyl-1-arylnaphth[1,2-e][1,3]oxazines}, url = {https://m2.mtmt.hu/api/publication/1013251}, author = {Szatmári, István and Martinek, Tamás and Lázár, László and Koch, A and Kleinpeter, E and Neuvonen, K and Fülöp, Ferenc}, doi = {10.1021/jo0355810}, journal-iso = {J ORG CHEM}, journal = {JOURNAL OF ORGANIC CHEMISTRY}, volume = {69}, unique-id = {1013251}, issn = {0022-3263}, abstract = {The disubstitution effects of X and Y in 1-(Y-phenyl)-3-(X- phenyl)-2,3-dihydro-1H-naphth[1,2-e][1,3]oxazines on the ring- chain tautomerism, the delocalization of the nitrogen lone pair (anomeric effect), and the C-13 NMR chemical shifts were analyzed by using multiple linear regression analysis. Study of the three-component equilibrium B reversible arrow A reversible arrow C revealed that the chain reversible arrow trans (A reversible arrow B) equilibrium constants are significantly influenced by the inductive effect (sigma(F)) of substituent Y on the 1-phenyl ring. In contrast, no significant substituent dependence on Y was observed for the chain reversible arrow cis (A reversible arrow C) equilibrium. There was an analogous dependence for the epimerization (C reversible arrow B) constants of 1-(Y-phenyl)-3-alkyl-2,3-dihydro-1H-naphth[1,2-e] [1,3]oxazines. With these model compounds, significant overlapping energies of the nitrogen lone pair was observed by NBO analysis in the trans forms B (to sigma*(C1-C1'), sigma*(C1- C10b), and sigma*(C3-O4)) and in the cis forms C (to sigma*(C1- H), sigma*(C1-C10b), and sigma*(C3-O4)). The effects of disubstitution revealed some characteristic differences between the cis and trans isomers. However, the results do not suggest that the anomeric effect predominates in the preponderance of the trans over the cis isomer. When the C-13 chemical shift changes induced Y by substituents X and Y (SCS) were subjected to multiple linear regression analysis, negative rho(F)(Y) and rho(F)(X) values were observed at C-1 and C-3 for both the cis and trans isomers. In contrast, the positive rho(R)(Y) values at C-1 and the negative rho(R)(X) values at C-3 observed indicated the contribution of resonance structures f (rho(R) > 0) and g (rho(R) < 0), respectively. The classical double bond-no-bond resonance structures proved useful in explaining the substituent sensitivities of the donation energies and the behavior of the SCS values.}, year = {2004}, eissn = {1520-6904}, pages = {3645-3653}, orcid-numbers = {Szatmári, István/0000-0002-8571-5229; Martinek, Tamás/0000-0003-3168-8066; Lázár, László/0000-0002-2135-8496; Fülöp, Ferenc/0000-0003-1066-5287} } @article{MTMT:1013250, title = {Transformation reactions of the Betti base analog aminonaphthols}, url = {https://m2.mtmt.hu/api/publication/1013250}, author = {Szatmári, István and Hetényi, Anasztázia and Lázár, László and Fülöp, Ferenc}, doi = {10.1002/jhet.5570410310}, journal-iso = {J HETEROCYCLIC CHEM}, journal = {JOURNAL OF HETEROCYCLIC CHEMISTRY}, volume = {41}, unique-id = {1013250}, issn = {0022-152X}, abstract = {By means of simple or domino ring-closure reactions of 1-(alpha-aminobenzyl)-2-naphthol (Betti base: 1), 1-aminomethyl-2-naplithol (2) and 2-(alpha-aminobenzyl)-1-naphthol (reverse Berri base: 3) with phosgene, ethyl benzimidate, 2-carboxybenzaldehyde, levulinic acid, salicylaldehyde/formalin or salicylaldehyde/acetaldehyde, naphth[1,2-e][1,3]oxazine and naphth[2,1-e][1,3]oxazine derivatives were prepared. All of the nitrogen-bridged polycyclic derivatives of 1 and 3 containing a number of centers of asymmetry were formed with nearly complete diastereoselectivity. Considerable differences were observed in the ring-closing abilities of the unsubstituted and phenyl-substituted aminonaphthols 1 and 2 and of the regioisomeric compounds 1 and 3.}, year = {2004}, eissn = {1943-5193}, pages = {367-373}, orcid-numbers = {Szatmári, István/0000-0002-8571-5229; Hetényi, Anasztázia/0000-0001-8080-6992; Lázár, László/0000-0002-2135-8496; Fülöp, Ferenc/0000-0003-1066-5287} }