TY - JOUR AU - Dembo, António AU - Ferenczi, Etelka AU - Jernei, Tamás AU - Bor, Andrea AU - Schelz, Zsuzsanna AU - Zupkó, István AU - Varga, Szilárd AU - Csámpai, Antal TI - CuAAC-Based Synthesis, Copper-Catalyzed Aldehyde-Forming Hydrolytic Fission and Antiproliferative Evaluation of Novel Ferrocenoylamino-Substituted Triazole-Tethered Quinine–Chalcone Hybrids JF - MOLECULES J2 - MOLECULES VL - 29 PY - 2024 IS - 2 PG - 23 SN - 1420-3049 DO - 10.3390/molecules29020375 UR - https://m2.mtmt.hu/api/publication/34499406 ID - 34499406 AB - A series of novel triazole-tethered ferrocenoylamino-substituted cinchona–chalcone hybrids along with two representative benzoylamino-substituted reference compounds were prepared by three methods of CuAAC chemistry. In line with the limited success or complete failure of attempted conversions with low catalyst loadings, by means of DFT modeling studies, we demonstrated that a substantial part of the Cu(I) ions can be chelated and thus trapped in the aroylamino-substituted cinchona fragment and all of the accessible coordinating sites of the chalcone residues. Accordingly, increased amounts of catalysts were used to achieve acceptable yields; however, the cycloadditions with para-azidochalcones were accompanied by partial or complete aldehyde-forming hydrolytic fission of the enone C=C bond in a substituent-, solvent- and copper load-dependent manner. The experienced hydrolytic stability of the hybrids obtained by cycloadditions with ortho-azidochalcones was interpreted in terms of relative energetics, DFT reactivity indices and MO analysis of simplified models of two isomer copper–enone complexes. The novel hybrids were evaluated on HeLa, MDA-MB-231 and A2780 cell lines and showed substantial activity at low-to-submicromolar concentrations. An organometallic model carrying 3,4,5-trimethoxyphenyl residue in the enone part with a para-disubstituted benzene ring in the central skeletal region was identified as the most potent antiproliferative lead, characterized by submicromolar IC50 values measured on the three investigated cells. The biological assays also disclosed that this ferrocenoylamino-containing lead compound displays a ca. two- to five-fold more substantial antiproliferative effect than its benzoylamino-substituted counterpart. LA - English DB - MTMT ER - TY - JOUR AU - Háznagy, Márton Benedek AU - Csámpai, Antal AU - Ugrai, Imre AU - Barnabás, Molnár AU - Matti, Haukka AU - Szakonyi, Zsolt TI - Stereoselective Synthesis and Catalytical Application of Perillaldehyde-Based 3-Amino-1,2-diol Regioisomers JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 8 PG - 25 SN - 1661-6596 DO - 10.3390/ijms25084325 UR - https://m2.mtmt.hu/api/publication/34791082 ID - 34791082 AB - A library of regioisomeric monoterpene-based aminodiols was synthesised and applied as chiral catalysts in the addition of diethylzinc to benzaldehyde. The synthesis of the first type of aminodiols was achieved starting from (−)-8,9-dihydroperillaldehyde via reductive amination, followed by Boc protection and dihydroxylation with the OsO4/NMO system. Separation of formed stereoisomers resulted in a library of aminodiol diastereoisomers. The library of regioisomeric analogues was obtained starting from (−)-8,9-dihydroperillic alcohol, which was transformed into a mixture of allylic trichloroacetamides via Overman rearrangement. Changing the protecting group to a Boc function, the protected enamines were subjected to dihydroxylation with the OsO4/NMO system, leading to a 71:16:13 mixture of diastereoisomers, which were separated, affording the three isomers in isolated form. The obtained primary aminodiols were transformed into secondary derivatives. The regioselectivity of the ring closure of the N-benzyl-substituted aminodiols with formaldehyde was also investigated, resulting in 1,3-oxazines in an exclusive manner. To explain the stability difference between diastereoisomeric 1,3-oxazines, a series of comparative theoretical modelling studies was carried out. The obtained potential catalysts were applied in the reaction of aromatic aldehydes and diethylzinc with moderate to good enantioselectivities (up to 94% ee), whereas the opposite chiral selectivity was observed between secondary aminodiols and their ring-closed 1,3-oxazine analogues. LA - English DB - MTMT ER - TY - JOUR AU - Szaniszló, Szebasztián AU - Csámpai, Antal AU - Horváth, Dániel AU - Tomecz, Richárd AU - Farkas, Viktor AU - Perczel, András TI - Unveiling the Oxazolidine Character of Pseudoproline Derivatives by Automated Flow Peptide Chemistry JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 8 SP - 4150 SN - 1661-6596 DO - 10.3390/ijms25084150 UR - https://m2.mtmt.hu/api/publication/34781847 ID - 34781847 AB - Pseudoproline derivatives such as Thr(ΨPro)-OH are commonly used in peptide synthesis to reduce the likelihood of peptide aggregation and to prevent aspartimide (Asi) formation during the synthesis process. In this study, we investigate notable by-products such as aspartimide formation and an imine derivative of the Thr(ΨPro) moiety observed in flow peptide chemistry synthesis. To gain insight into the formation of these unexpected by-products, we design a series of experiments. Furthermore, we demonstrate the oxazolidine character of the pseudoproline moiety and provide plausible mechanisms for the two-way ring opening of oxazolidine leading to these by-products. In addition, we present evidence that Asi formation appears to be catalyzed by the presence of the pseudoproline moiety. These observed side reactions are attributed to elevated temperature and pressure; therefore, caution is advised when using ΨPro derivatives under such harsh conditions. In addition, we propose a solution whereby thermodynamically controlled Asi formation can be kinetically prevented. LA - English DB - MTMT ER - TY - JOUR AU - Murányi, József AU - Jernei-Duró, Cintia AU - Gurbi, Bianka AU - Móra , István András AU - Varga, Attila AU - Németh, Krisztina AU - Simon, József AU - Csala, Miklós AU - Csámpai, Antal TI - Novel Erlotinib–Chalcone Hybrids Diminish Resistance in Head and Neck Cancer by Inducing Multiple Cell Death Mechanisms JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 4 PG - 18 SN - 1661-6596 DO - 10.3390/ijms24043456 UR - https://m2.mtmt.hu/api/publication/33635331 ID - 33635331 AB - In a search for novel therapeutic options for head and neck squamous cell carcinomas (HNSCCs) generally treated with limited therapeutic success, we synthesized a series of novel erlotinib–chalcone molecular hybrids with 1,2,3-triazole and alkyne linkers and evaluated them for their anticancer activity on Fadu, Detroit 562 and SCC-25 HNSCC cell lines. Time- and dose-dependent cell viability measurements disclosed a significantly increased efficiency of the hybrids compared to the 1:1 combination of erlotinib and a reference chalcone. The clonogenic assay demonstrated that hybrids eradicate HNSCC cells in low micromolar concentrations. Experiments focusing on potential molecular targets indicate that the hybrids trigger the anticancer effect by a complementary mechanism of action that is independent of the canonical targets of their molecular fragments. Confocal microscopic imaging and real-time apoptosis/necrosis detection assay pointed to slightly different cell death mechanisms induced by the most prominent triazole- and alkyne-tethered hybrids (6a and 13, respectively). While 6a featured the lowest IC50 values on each of the three HNSCC cell lines, in Detroit 562 cells, this hybrid induced necrosis more markedly compared to 13. The therapeutic potential indicated by the observed anticancer efficacy of our selected hybrid molecules validates the concept of development and justifies further investigation to reveal the underlying mechanism of action. LA - English DB - MTMT ER - TY - JOUR AU - Varga, István AU - Goldschmidt Gőz, Viktória AU - Pintér, István AU - Csámpai, Antal AU - Perczel, András TI - Acetyl group for proper protection of β-sugar-amino acids used in SPPS JF - AMINO ACIDS J2 - AMINO ACIDS VL - 55 PY - 2023 SP - 969 EP - 979 PG - 11 SN - 0939-4451 DO - 10.1007/s00726-023-03278-1 UR - https://m2.mtmt.hu/api/publication/34036752 ID - 34036752 N1 - Laboratory of Structural Chemistry and Biology, Institute of Chemistry, Eötvös Loránd University, Pázmány P. Stny. 1/A, Budapest, 1117, Hungary György Hevesy Doctoral School of Chemistry, Eötvös Loránd University, Budapest, Hungary ELKH-ELTE Protein Modeling Research Group, Pázmány P. Stny. 1/A, Budapest, 1117, Hungary Organic Chemistry Department, Eötvös Loránd University, Pázmány P. Stny. 1/A, Budapest, 1117, Hungary Export Date: 2 October 2023 CODEN: AACIE Correspondence Address: Perczel, A.; Laboratory of Structural Chemistry and Biology, Pázmány P. Stny. 1/A, Hungary; email: perczel.andras@ttk.elte.hu AB - The synthesis of d- glucosamine-1-carboxylic acid based β-sugar amino acids (β-SAAs) is typically performed in nine consecutive steps via an inefficient OAc → Br → CN conversion protocol with low overall yield. Here, we present the improved and more efficient synthesis of both Fmoc-GlcAPC-OH and Fmoc-GlcAPC(Ac)-OH, β-SAAs consisting of only 4–5 synthetic steps. Their active ester and amide bond formation with glycine methyl ester (H-Gly-OMe) was completed and monitored by 1 H NMR. The stability of the pyranoid OHs protecting the acetyl groups was investigated under three different Fmoc cleavage conditions and was found to be satisfactory even at high piperidine concentration (e.g. 40%). We designed a SPPS protocol using Fmoc-GlcAPC(Ac)-OH to produce model peptides Gly-β-SAA-Gly as well as Gly-β-SAA-β-SAA-Gly with high coupling efficiency. The products were deacetylated using the Zemplén method, which allows the hydrophilicity of a building block and/or chimera to be fine-tuned, even after the polypeptide chain has already been synthesized. LA - English DB - MTMT ER - TY - JOUR AU - Alaoui, Nour-Eddine El AU - Boulhaoua, Mohammed AU - Hutai, Dániel Gábor AU - Szabó, Rita (Oláhné) AU - Bősze, Szilvia AU - Hudecz, Ferenc AU - Csámpai, Antal TI - Synthetic and DFT Modeling Studies on Suzuki–Miyaura Reactions of 4,5-Dibromo-2-methylpyridazin-3(2H)-one with Ferrocene Boronates, Accompanied by Hydrodebromination and a Novel Bridge-Forming Annulation In Vitro Cytotoxic Activity of the Ferrocenyl–Pyridazinone Products JF - CATALYSTS J2 - CATALYSTS VL - 12 PY - 2022 IS - 6 PG - 21 SN - 2073-4344 DO - 10.3390/catal12060578 UR - https://m2.mtmt.hu/api/publication/32847481 ID - 32847481 LA - English DB - MTMT ER - TY - JOUR AU - Czuczi, Tamás AU - Murányi, József AU - Bárány, Péter Tibor AU - Móra , István András AU - Borbély, Adina Noémi AU - Csala, Miklós AU - Csámpai, Antal TI - Synthesis and Antiproliferative Activity of Novel Imipridone–Ferrocene Hybrids with Triazole and Alkyne Linkers JF - PHARMACEUTICALS J2 - PHARMACEUTICALS-BASE VL - 15 PY - 2022 IS - 4 PG - 19 SN - 1424-8247 DO - 10.3390/ph15040468 UR - https://m2.mtmt.hu/api/publication/32782717 ID - 32782717 LA - English DB - MTMT ER - TY - PAT AU - Csámpai, Antal AU - Bárány, Péter Tibor AU - Czuczi, Tamas AU - Kovacs, Imre AU - Adamis, Balint AU - Nemeth, Zsofia AU - Murányi, József AU - Olahne, Szabo Rita AU - Bosze, Szilvia AU - Mezo, Gabor AU - Kőhidai, László AU - Lajkó, Eszter AU - Takács, Angéla AU - Láng, Orsolya AU - Mezo, Diana TI - Synthesis of novel imipridone derivatives and their evaluation for their anticancer activity.. WO2022029459A1 TS - WO2022029459A1 PY - 2022 SP - 91pp. PG - 91 UR - https://m2.mtmt.hu/api/publication/32683354 ID - 32683354 AB - The present invention relates to compds. of formula (I) (I) or pharmaceutically acceptable salts, and stereoisomers thereof, including enantiomers, racemic mixts., mixts. of enantiomers, or combinations thereof, which are applicable for use in treating cancer diseases. The present invention further relates to a pharmaceutical compn. comprising the above compds. [on SciFinder(R)] LA - English DB - MTMT ER - TY - CHAP AU - Csámpai, Antal AU - Fodor, Kinga Judit AU - Hutai, Dániel Gábor AU - Jernei, Tamás AU - Sulyok-Eiler, Máté AU - Harmat, Veronika TI - Részlegesen telített polikondenzált indolszármazékok szintézise és szerkezetanalízise, a diasztereoszelektív reakciólépések mechanizmusának elméleti modellezése. T2 - Vegyészkonferencia 2022 PB - Magyar Kémikusok Egyesülete (MKE) CY - Budapest SN - 9786156018113 PY - 2022 UR - https://m2.mtmt.hu/api/publication/33053795 ID - 33053795 LA - Hungarian DB - MTMT ER - TY - PAT AU - Csámpai, Antal AU - Bárány, Péter Tibor AU - CZUCZI, TAMÁS AU - KOVÁCS, IMRE AU - ADAMIS, BÁLINT AU - NÉMETH, ZSÓFIA AU - Murányi, József AU - Szabó, Rita (Oláhné) AU - Bősze, Szilvia AU - Mező, Gábor AU - KŐHIDAI, LÁSZLÓ AU - LAJKÓ, ESZTER AU - TAKÁCS, ANGÉLA AU - LÁNG, ORSOLYA AU - MEZŐ, DIÁNA TI - SYNTHESIS OF NOVEL IMIPRIDONE DERIVATIVES AND THEIR EVALUATION FOR THEIR ANTICANCER ACTIVITY PY - 2022 UR - https://m2.mtmt.hu/api/publication/32787939 ID - 32787939 LA - English DB - MTMT ER -