Neutron activation of In(iii) complexes with thiosemicarbazones leads to the production of potential radiopharmaceuticals for the treatment of breast cancer. (27th July 2017)

• Record Type: Journal Article
• 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
• Is Part Of: New journal of chemistry. Volume 41:Number 17(2017)
• Page Start: 9041
• Page End: 9050
• Publication Date: 2017-07-27
• Subjects: Chemistry -- Periodicals; Chimie -- Périodiques; 540
• DOI: 10.1039/c7nj01547j
• Languages: English
• ISSNs: 1144-0546

Abstract

Abstract : 114m In(iii ) complexes with 2-acetylpyridine-derived thiosemicarbazones show potent cytotoxic activity. Abstract : In(iii ) complexes [In(2Ac4 o ClPh)2 ]NO3 (1 ) and [In(2Ac4 p FPh)2 ]NO3 ·1.5H2 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)Cl2 (MeOH)] (3 ) and [In(2Ac4 p FPh)Cl2 (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 IC50 MRC-5 /IC50 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.