26th International Symposium on Analytical and Environmental Problems 284 EFFECTS OF STEPWISE TERMINAL NH2-METHYLATION OF ESTRONE- SALICYLALDEHYDE–THIOSEMICARBAZONE AND COPPER COORDINATION, SOLUTION SPECIATION, ANTICANCER ACTIVITY AND REDOX ACTIVITY. Tatsiana V. Petrasheuskaya, 1,2 Debora Wernitznig, 3 Márton A. Kiss, 4 Nóra V. May, 5 Dominik Wenisch, 3 Bernhard K. Keppler, 3 Éva Frank, 4 Éva A. Enyedy 1,2 1 Department of Inorganic and Analytical Chemistry, Interdisciplinary Excellence Centre, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary. Email: enyedy@chem.u-szeged.hu 2 MTA-SZTE Lendület Functional Metal Complexes Research Group, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary 3 Institute of Inorganic Chemistry and Research Cluster ‘Translational Cancer Therapy Research’, University of Vienna, Währinger Straße 42, Vienna, Austria 4 Department of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary 5 Chemical Crystallography Research Laboratory, Research Centre for Natural Sciences, Magyar tudósok körútja 2, H-1117 Budapest, Hungary petrashevtanya@chem.u-szeged.hu Thiosemicarbazones (TSCs) as excellent metal chelators are a class of organic compounds with structural diversity and broad spectrum of pharmacological activities, such as antiproliferative, antiviral, antibacterial, antimalarial and antifungal effect [1]. Also, their metal complex can be more active than the free ligand, and some side effects may decrease upon complexation. In addition, the complex can exhibit bioactivities, which are not shown by the free ligand. Previously, a tridentate estrone-salicylaldehyde TSC hybrid molecule (estrone- TSC) was developed in addition to an analogous bicyclic derivative (thn-TSC), which were cytotoxic against the hormone-responsive MCF-7 breast cancer cell lines (IC50: thn-TSC: 3.7 μM, estrone-TSC: 6.4 μM). Their Cu(II) complexes showed more significant cytotoxicity than the ligands as 1-2 orders of magnitude lower IC50 values were obtained for the complexes against a series of human cancer cell lines [2]. Disubstitution of the terminal NH2 groups in case of several α-N-pyridine thiosemicarbazones could result in highly increased anticancer activity (e.g. dimethylated Triapine, DpC, Dp44mT) [3]. Based on this finding in this work the N-terminally mono- and dimethylated derivatives of estrone-TSC and thn-TSC (Chart 1) and their Cu(II) complexes were aimed to prepare to obtain more effective compounds. Chart 1. Chemical structures of the investigated ligands. Me-thn-TSC Me 2 -thn-TSC Me-estrone-TSC Me 2 - estrone-TSC