Neutron activation of In(iii) complexes with thiosemicarbazones leads to the production of potential radiopharmaceuticals for the treatment of breast cancerElectronic supplementary information (ESI) available: FT-IR spectra of ligand H2Ac4oClPh and complex (1), as well as their 1H and 13C{1H} NMR spectra together with the 2D COSY, HMQC and HMBC contour maps used to support the 1H and 13C attributions; X-ray crystallography data and the high resolution mass spectra [ESI(+), IT-TOF] of 1 and 2; an

• Main Authors: Oliveira, Alexandre A, Franco, Lucas L, dos Santos, Raquel G, Perdigão, Gabriele M. C, da Silva, Jeferson G, Souza-Fagundes, Elaine M, Beraldo, Heloisa
• Format: Article
• Language: English
• ISSN: 1144-0546; 1369-9261
• DOI: 10.1039/c7nj01547j

In( iii ) complexes [In(2Ac4 o ClPh) 2 ]NO 3 ( 1 ) and [In(2Ac4 p FPh) 2 ]NO 3 ·1.5H 2 O ( 2 ) were obtained with N (4)- ortho -chlorophenyl-2-acetylpyridine thiosemicarbazone (H2Ac4 o ClPh) and N (4)- para -fluorophenyl-2-acetylpyridine thiosemicarbazone (H2Ac4 p FPh). Neutron activation of complexes ( 1 ) and ( 2 ), and of previously prepared [In(2Ac4 o ClPh)Cl 2 (MeOH)] ( 3 ) and [In(2Ac4 p FPh)Cl 2 (MeOH)] ( 4 ) resulted in the formation of 114m In/ 115m In analogues ( *1-*4 ). The cytotoxic activities of the compounds under study were investigated on MCF-7 breast cancer cells as well as against non-malignant MRC-5 fibroblast cells. Upon coordination to In( iii ) the cytotoxicity against MCF-7 cells significantly increased in complexes ( 1-4 ), suggesting that complexation was a good strategy to improve the cytotoxic effect. While both non-radioactive and radioactive In( iii ) salts were inactive against MCF-7 cells, the radioactive complexes ( *1-*4 ) proved to be 10 2 to 10 4 times more potent than the non-radioactive analogues ( 1-4 ). For the non-radioactive In( iii ) complexes ( 1-4 ) the selectivity indexes (SI), defined as IC 50 MRC-5 /IC 50 MCF-7 , were SI = 0.07-0.36, while high values of SI were found for the radioactive In( iii ) analogues ( *1-*4 ), SI = 46-4716, indicating that irradiation represented an interesting strategy for increasing the selectivity. Since cytotoxicity was evaluated following 48 h of treatment and 72 h after neutron activation, the observed cytotoxic effects were attributed mainly to 114m In, the contribution of the 115m In ( t 1/2 = 4.5 h) isomer being considered irrelevant. Complexes ( *1-*4 ) induced higher levels of intracellular ROS in MCF-7 cells in comparison to the parent compounds. The results suggest that 114m In complexes with thiosemicarbazones might show potential for application as radiopharmaceuticals for the treatment of breast cancer. 114m In( iii ) complexes with 2-acetylpyridine-derived thiosemicarbazones show potent cytotoxic activity.