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Synthesis, Characterization, and In Vivo Anti-Cancer Activity of New Metal Complexes Derived from Isatin-N(4)antipyrinethiosemicarbazone Ligand Against Ehrlich Ascites Carcinoma Cells

1
Department of Chemistry, Faculty of Science, Menoufia University, Shebin El-Koom 32512, Egypt
2
Biochemistry Division, Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Koom 32512, Egypt
3
Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, Okayama 7008530, Japan
4
Department of Molecular Biology, Genetic Engineering & Biotechnology Institute, University of Sadat City, Sadat City 32958, Egypt
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Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE 106 91 Stockholm, Sweden
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Department of Experimental Cancer Medicine (ECM); Novum, 14157 Huddinge, Stockholm, Sweden
7
Pharmacognosy Group, Department of Medicinal Chemistry, Uppsala University, Biomedical Centre, Box 574, SE-751 23 Uppsala, Sweden
8
International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China
9
Al-Rayan Research and Innovation Center, Al-Rayan Colleges, Medina 42541, Saudi Arabia
*
Authors to whom correspondence should be addressed.
Molecules 2019, 24(18), 3313; https://doi.org/10.3390/molecules24183313
Received: 18 July 2019 / Revised: 7 September 2019 / Accepted: 9 September 2019 / Published: 11 September 2019
The current study aimed to synthesize new metal coordination complexes with potential biomedical applications. Metal complexes were prepared via the reaction of isatin-N(4)anti- pyrinethiosemicarbazone ligand 1 with Cu(II), Ni(II), Co(II), Zn(II), and Fe(III) ions. The obtained metal complexes 212 were characterized using elemental, spectral (1H-NMR, EPR, Mass, IR, UV-Vis) and thermal (TGA) techniques, as well as magnetic moment and molar conductance measurements. In addition, their geometries were studied using EPR and UV–Vis spectroscopy. To evaluate the in vivo anti-cancer activities of these complexes, the ligand 1 and its metal complexes 2, 7 and 9 were tested against solid tumors. The solid tumors were induced by subcutaneous (SC) injection of Ehrlich ascites carcinoma (EAC) cells in mice. The impact of the selected complexes on the reduction of tumor volume was determined. Also, the expression levels of vascular endothelial growth factor (VEGF) and cysteine aspartyl-specific protease-7 (caspase-7) in tumor and liver tissues of mice bearing EAC tumor were determined. Moreover, their effects on alanine transaminase (ALT), aspartate transaminase (AST), albumin, and glucose levels were measured. The results revealed that the tested compounds, especially complex 9, reduced tumor volume, inhibited the expression of VEGF, and induced the expression of caspase-7. Additionally, they restored the levels of ALT, AST, albumin, and glucose close to their normal levels. Taken together, our newly synthesized metal complexes are promising anti-cancer agents against solid tumors induced by EAC cells as supported by the inhibition of VEGF and induction of caspase-7. View Full-Text
Keywords: metal complexes; isatin-N(4)antipyrinethiosemicarbazone; Ehrlich ascites carcinoma; tumor volume; VEGF; caspase-7 metal complexes; isatin-N(4)antipyrinethiosemicarbazone; Ehrlich ascites carcinoma; tumor volume; VEGF; caspase-7
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El-Saied, F.; El-Aarag, B.; Salem, T.; Said, G.; Khalifa, S.A.M.; El-Seedi, H.R. Synthesis, Characterization, and In Vivo Anti-Cancer Activity of New Metal Complexes Derived from Isatin-N(4)antipyrinethiosemicarbazone Ligand Against Ehrlich Ascites Carcinoma Cells. Molecules 2019, 24, 3313.

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