TY - JOUR AU - Szatmári, István AU - Fülöp, Ferenc TI - Syntheses, transformations and applications of aminonaphthol derivatives prepared via modified Mannich reactions JF - TETRAHEDRON J2 - TETRAHEDRON VL - 69 PY - 2013 IS - 4 SP - 1255 EP - 1278 PG - 24 SN - 0040-4020 DO - 10.1016/j.tet.2012.11.055 UR - https://m2.mtmt.hu/api/publication/2221504 ID - 2221504 N1 - Cited By :61 Export Date: 15 October 2021 CODEN: TETRA Correspondence Address: Fülöp, F.; Institute of Pharmaceutical Chemistry, Eötvös u. 6, H-6720 Szeged, Hungary; email: fulop@pharm.u-szeged.hu Chemicals/CAS: imine, 13774-92-0 LA - English DB - MTMT ER - TY - JOUR AU - Gyemant, N AU - Engi, Helga AU - Schelz, Zsuzsanna AU - Szatmári, István AU - Toth, D AU - Fülöp, Ferenc AU - Molnár, József AU - de Witte, PAM TI - In vitro and in vivo multidrug resistance reversal activity by a Betti-base derivative of tylosin JF - BRITISH JOURNAL OF CANCER J2 - BRIT J CANCER VL - 103 PY - 2010 IS - 2 SP - 178 EP - 185 PG - 8 SN - 0007-0920 DO - 10.1038/sj.bjc.6605716 UR - https://m2.mtmt.hu/api/publication/1365862 ID - 1365862 AB - 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 LA - English DB - MTMT ER - TY - JOUR AU - Heydenreich, M AU - Koch, A AU - Klod, S AU - Szatmári, István AU - Fülöp, Ferenc AU - Kleinpeter, E TI - 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 JF - TETRAHEDRON J2 - TETRAHEDRON VL - 62 PY - 2006 IS - 48 SP - 11081 EP - 11089 PG - 9 SN - 0040-4020 DO - 10.1016/j.tet.2006.09.037 UR - https://m2.mtmt.hu/api/publication/1078937 ID - 1078937 N1 - Univ Potsdam, Inst Chem, D-14415 Potsdam, Germany. Univ Szeged, Hungarian Acad Sci, Res Grp Heterocycl Chem, H-6701 Szeged, Hungary. Univ Szeged, Inst Pharmaceut Chem, H-6701 Szeged, Hungary. AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Szatmári, István AU - Martinek, Tamás AU - Lázár, László AU - Koch, A AU - Kleinpeter, E AU - Neuvonen, K AU - Fülöp, Ferenc TI - 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 JF - JOURNAL OF ORGANIC CHEMISTRY J2 - J ORG CHEM VL - 69 PY - 2004 IS - 11 SP - 3645 EP - 3653 PG - 9 SN - 0022-3263 DO - 10.1021/jo0355810 UR - https://m2.mtmt.hu/api/publication/1013251 ID - 1013251 AB - 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. LA - English DB - MTMT ER - TY - JOUR AU - Szatmári, István AU - Hetényi, Anasztázia AU - Lázár, László AU - Fülöp, Ferenc TI - Transformation reactions of the Betti base analog aminonaphthols JF - JOURNAL OF HETEROCYCLIC CHEMISTRY J2 - J HETEROCYCLIC CHEM VL - 41 PY - 2004 IS - 3 SP - 367 EP - 373 PG - 7 SN - 0022-152X DO - 10.1002/jhet.5570410310 UR - https://m2.mtmt.hu/api/publication/1013250 ID - 1013250 AB - 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. LA - English DB - MTMT ER -