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Anticancer Effects of Heterocyclic Schiff Base Ligands and Their Metal Complexes on Leukemia Cells

Author(s): B. Shekhany*, F. Ozer, E. Aytar, S. W. Bradosty, M. U. Boyraz, A. O. Gurol, F. K. Shaikh and F. Suzergoz
Departmnet of Biology Science Art Faculty, University of Harran, Sanliurfa 63510, Turkey, 1Department of Medical Laboratory, Technology Shaqlawa Technical College, Erbil Polytechnic University, Erbil 44001, Iraq, 2Departmnet of Chemistry, 3Department of Histology and Embriology, Science Art Faculty, University of Harran, Sanliurfa 63510, 4Department of Immunology, Aziz Sancar Institute of Experimental Medicine, 5Department of Medical Pharmacology, Istanbul Medical Faculty, University of Istanbul, Istanbul 34452, Turkey, 6Centre for Biotechnology, Pravara Institutes of Medical Sciences (DU), Loni 413736, Maharashtra, India

Correspondence Address:
B. Shekhany, Departmnet of Biology Science Art Faculty, University of Harran, Sanliurfa 63510, Turkey, E-mail:

Chemotherapy is one of the most important treatment options in the treatment of all types of leukemia, but multi-drug resistance often precludes the success of this treatment. In this study, anticancer properties of heterocyclic salicylaldimines and their Cu(II) complexes on K562 human chronic myelogenous leukemia cell line were investigated. Doxorubicin was used as positive control. Compounds (C1-8 and doxorubicin) were placed to 96-well culture plate in triplicate order at doses of 1, 10, 100, 1000 μM and then K562 cells were seeded into the wells at the dose of 105/ml. After 72 h incubation, colorimetric 3-[4,5-dimethylthiazol-2- yl]-2,5 diphenyl tetrazolium bromide test was performed to determine half-maximal inhibitory concentration values of each compound. Antiproliferative effects of compounds were determined using carboxyfluorescein succinimidyl ester assay. Apoptosis induction potential of each compound determined by mitochondrial membrane potential analysis (Rho123), cleaved caspase-3 expression analysis by flow cytometry and immunofluorescent staining and cell morphology analysis by giemza, hematoxylin and eosin and Papanicolaou protocols. The metal complexes of the compounds had stronger cytotoxic effects and cleaved caspase-3 expression than their ligands. Mitochondrial membrane potential was found at low levels in cells treated with Schiff base compounds and doxorubicin. In the cell morphology analyzes, chromatin condensation and marginalization, changes in the cell membrane, ghost cells and apoptotic bodies were observed as evidence of apoptosis formation. Among the tested heterocyclic Schiff base compounds, the powerful cytotoxic and apoptosis-inducing potential of Bis((9-((cycloheptylimino)methyl)-1,1,7,7-tetramethyl-2,3,6,7-tetrahydro- 1H,5H-pyrido[3,2,1-ij]quinolin-8-yl)oxy)copper complex (C6) draws attention as a promising compounds withal a need for further in vitro and in vivo studies.

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