TY - JOUR AU - Kovács, Ferenc AU - Huliák, Ildikó AU - Árva, Hédi AU - Csontné Kiricsi, Mónika AU - Erdős, Dóra AU - Kocsis, Marianna AU - Takács, Gergely AU - Balogh, György Tibor AU - Nagyné Frank, Éva TI - Medicinal-Chemistry-Driven Approach to 2-Substituted Benzoxazole–Estradiol Chimeras: Synthesis, Anticancer Activity, and Early ADME Profile JF - CHEMMEDCHEM J2 - CHEMMEDCHEM VL - 18 PY - 2023 IS - 22 PG - 9 SN - 1860-7179 DO - 10.1002/cmdc.202300352 UR - https://m2.mtmt.hu/api/publication/34147665 ID - 34147665 N1 - Department of Molecular and Analytical Chemistry, University of Szeged, Dóm tér 7–8, Szeged, 6720, Hungary Department of Biochemistry and Molecular Biology, Doctoral School of Biology, University of Szeged, Közép fasor 52, Szeged, 6726, Hungary Department of Chemical and Environmental Process Engineering, Budapest University of Technology and Economics, Műegyetem rkp. 3, Budapest, 1111, Hungary Mcule.com Kft., Bartók Béla út 105–113, Budapest, 1115, Hungary Department of Pharmaceutical Chemistry, Semmelweis University, Hőgyes E. 9, Budapest, 1085, Hungary Export Date: 13 October 2023 CODEN: CHEMG Correspondence Address: Frank, É.; Department of Molecular and Analytical Chemistry, Dóm tér 7–8, Hungary; email: frank@chem.u-szeged.hu Correspondence Address: Balogh, G.T.; Department of Chemical and Environmental Process Engineering, Műegyetem rkp. 3, Hungary; email: balogh.gyorgy.tibor@semmelwies.hu AB - The efficient synthesis of novel estradiol‐based A‐ring‐fused oxazole derivatives, which can be considered as benzoxazole‐steroid domain‐integrated hybrids containing a common benzene structural motif, is described. The target compounds were prepared from steroidal 2‐aminophenol precursors by heterocycle formation or functional group interconversion (FGI) strategies. According to 2D projection‐based t‐distributed stochastic neighbor embedding (t‐SNE), the novel molecules were proved to represent a new chemical space among steroid drugs. They were characterized based on critical physicochemical parameters using in silico and experimental data. The performance of the compounds to inhibit cell proliferation was tested on four human cancer cell lines and non‐cancerous cells. Further examinations were performed to reveal IC50 and lipophilic ligand efficiency (LLE) values, cancer cell selectivity, and apoptosis‐triggering features. Pharmacological tests and LLE metric revealed that some derivatives, especially the 2‐(4‐ethylpiperazin‐1‐yl)oxazole derivative exhibit strong anticancer activity and trigger the apoptosis of cancer cells with relatively low promiscuity risk similarly to the structurally most closely‐related and intensively studied anticancer agent, 2‐methoxy‐estradiol. LA - English DB - MTMT ER - TY - JOUR AU - Takács, Gergely AU - Havasi, Dávid AU - Sándor, Márk AU - Dohánics, Zsolt AU - Balogh, György Tibor AU - Kiss, Róbert TI - DIY Virtual Chemical Libraries - Novel Starting Points for Drug Discovery JF - ACS MEDICINAL CHEMISTRY LETTERS J2 - ACS MED CHEM LETT VL - 14 PY - 2023 IS - 9 SP - 1188 EP - 1197 PG - 10 SN - 1948-5875 DO - 10.1021/acsmedchemlett.3c00146 UR - https://m2.mtmt.hu/api/publication/34119941 ID - 34119941 LA - English DB - MTMT ER - TY - JOUR AU - Vincze, Anna AU - Dékány, Gergely AU - Bicsak, Richárd AU - Formanek, András AU - Moreau, Yves AU - Koplányi, Gábor AU - Takács, Gergely AU - Katona, Gábor AU - Balogh Weiser, Diána AU - Arany, Ádám AU - Balogh, György Tibor TI - Natural Lipid Extracts as an Artificial Membrane for Drug Permeability Assay: In Vitro and In Silico Characterization JF - PHARMACEUTICS J2 - PHARMACEUTICS VL - 15 PY - 2023 IS - 3 PG - 19 SN - 1999-4923 DO - 10.3390/pharmaceutics15030899 UR - https://m2.mtmt.hu/api/publication/33692858 ID - 33692858 N1 - Funding Agency and Grant Number: Richter Gedeon Excellence PhD Scholarship from the Richter Gedeon Foundation [BO/00175/21]; Hungarian Academy of Sciences Funding text: This project was supported by the Central Europe Leuven Strategic Alliance (CELSA-2021/019) and by an FK-137582 grant from the National Research and Innovation Office, Hungary (NRDI). AB - In vitro non-cellular permeability models such as the parallel artificial membrane permeability assay (PAMPA) are widely applied tools for early-phase drug candidate screening. In addition to the commonly used porcine brain polar lipid extract for modeling the blood–brain barrier’s permeability, the total and polar fractions of bovine heart and liver lipid extracts were investigated in the PAMPA model by measuring the permeability of 32 diverse drugs. The zeta potential of the lipid extracts and the net charge of their glycerophospholipid components were also determined. Physicochemical parameters of the 32 compounds were calculated using three independent forms of software (Marvin Sketch, RDKit, and ACD/Percepta). The relationship between the lipid-specific permeabilities and the physicochemical descriptors of the compounds was investigated using linear correlation, Spearman correlation, and PCA analysis. While the results showed only subtle differences between total and polar lipids, permeability through liver lipids highly differed from that of the heart or brain lipid-based models. Correlations between the in silico descriptors (e.g., number of amide bonds, heteroatoms, and aromatic heterocycles, accessible surface area, and H-bond acceptor–donor balance) of drug molecules and permeability values were also found, which provides support for understanding tissue-specific permeability. LA - English DB - MTMT ER - TY - JOUR AU - Sanchez-Garcia, Ruben AU - Havasi, Dávid AU - Takács, Gergely AU - Robinson, Matthew C. AU - Lee, Alpha AU - von Delft, Frank AU - Deane, Charlotte M. TI - CoPriNet: graph neural networks provide accurate and rapid compound price prediction for molecule prioritisation JF - Digital Discovery J2 - Digital Discovery VL - 2 PY - 2023 IS - 1 SP - 103 EP - 111 PG - 9 SN - 2635-098X DO - 10.1039/D2DD00071G UR - https://m2.mtmt.hu/api/publication/33645504 ID - 33645504 N1 - Department of Statistics, University of Oxford, Oxford, OX1 3LB, United Kingdom Structural Genomics Consortium (SGC), University of Oxford, Oxford, OX3 7DQ, United Kingdom Mcule.com Kft, Bartók Béla út 105-113, Budapest, 1115, Hungary Department of Chemical and Environmental Process Engineering, Budapest University of Technology and Economics, Müegyetem rakpart 3, Budapest, 1111, Hungary PostEra Inc., 1209 Orange Street, Wilmington, DE 19801, United States Department of Physics, University of Cambridge, Cambridge, CB3 0HE, United Kingdom Diamond Light Source, Didcot, OX11 0DE, United Kingdom Department of Biochemistry, University of Johannesburg, Johannesburg, 2006, South Africa Export Date: 7 September 2023 Correspondence Address: Sanchez-Garcia, R.; Department of Statistics, United Kingdom; email: ruben.sanchez-garcia@stats.ox.ac.uk Correspondence Address: von Delft, F.; Structural Genomics Consortium (SGC), United Kingdom Correspondence Address: Deane, C.M.; Department of Statistics, United Kingdom; email: deane@stats.ox.ac.uk AB - CoPriNet can predict compound prices after being trained on 6M pairs of compounds and prices collected from the Mcule catalogue. LA - English DB - MTMT ER - TY - CHAP AU - Hunyadi, Attila AU - Agbadua, Orinamhe Godwin AU - Takács, Gergely AU - Balogh, György Tibor ED - Litwack, G. TI - Scavengome of an antioxidant T2 - Antioxidants PB - Academic Press CY - Cambridge SN - 9780443157684 T3 - VITAMINS AND HORMONES-ADVANCES IN RESEARCH AND APPLICATIONS, ISSN 0083-6729 ; 121. PY - 2023 SP - 81 EP - 108 PG - 28 DO - 10.1016/bs.vh.2022.09.003 UR - https://m2.mtmt.hu/api/publication/33282190 ID - 33282190 N1 - Institute of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, Szeged, Hungary Interdisciplinary Centre for Natural Products, University of Szeged, Szeged, Hungary Department of Chemical and Environmental Process Engineering, Budapest University of Technology and Economics, Budapest, Hungary Mcule.com Ltd., Budapest, Hungary Department of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, Hungary Export Date: 29 November 2022 CODEN: VIHOA Correspondence Address: Hunyadi, A.; Institute of Pharmacognosy, Hungary; email: hunyadi.attila@szte.hu LA - English DB - MTMT ER - TY - GEN AU - Sanchez-Garcia, Ruben AU - Havasi, Dávid AU - Takács, Gergely AU - Robinson, Matthew C AU - Lee, Alpha AU - von Delft, Frank AU - Deane, Charlotte M TI - CoPriNet: Deep learning compound price prediction for use in de novo molecule generation and prioritization. PY - 2022 UR - https://m2.mtmt.hu/api/publication/32740866 ID - 32740866 LA - English DB - MTMT ER - TY - JOUR AU - Takács, Gergely AU - Sándor, Márk AU - Szalai, Zoltán AU - Kiss, Róbert AU - Balogh, György Tibor TI - Analysis of the uncharted, druglike property space by self-organizing maps JF - MOLECULAR DIVERSITY J2 - MOL DIVERS VL - 26 PY - 2022 IS - 5 SP - 2427 EP - 2441 PG - 15 SN - 1381-1991 DO - 10.1007/s11030-021-10343-y UR - https://m2.mtmt.hu/api/publication/32470850 ID - 32470850 LA - English DB - MTMT ER -