ABSTRACT
Breast cancer is the most dangerous type in women and its fatality rate has increased over the past decade. To develop more potent and target-specific breast cancer drugs, six arene ruthenium(II) complexes (1-6) containing naphthoyl benzhydrazine ligands (NL1-NL3) were synthesized and characterized by analytical and spectroscopic (infrared, UV-visible, NMR and HR-MS) methods. The SC-XRD analysis of 1 and 6 demonstrates the bis N^O bidentate binding nature of ligands to ruthenium ions and a pseudo-octahedral geometry around the Ru(II) ion. Solution stability studies using UV-Vis spectroscopy evidenced the instantaneous hydrolysis of the complexes to form monoaquated species in a solution of 1 : 9 (v/v) DMSO/phosphate buffer. All the complexes were screened for their in vitro antiproliferative activities against different human breast cancer cells, including MCF-7, SkBr3, MDA-MB-468, MDA-MB-231, and non-cancerous HEK-293 cells, by an MTT assay, and they displayed good cancer cell growth inhibitory capacity with low IC50 values. Notably, complexes 2 and 5 comprising methoxy and p-cymene groups exhibited excellent cytotoxicity towards SkBr3 cells compared to clinical drug cisplatin. AO-EB and HOECHST-33342 staining assays revealed apoptotic morphological changes in complex-treated cancer cells. Further, reactive oxygen species and mitochondrial membrane potential assays validated that the complexes induce apoptotic cell death via an intrinsic mitochondrial pathway with ROS production. In addition, the apoptotic induction and the quantification of late apoptosis were established with the aid of western blot and flow cytometry analysis, respectively.
Subject(s)
Antineoplastic Agents , Breast Neoplasms , Coordination Complexes , Ruthenium , Humans , Female , Cell Line, Tumor , Breast Neoplasms/drug therapy , Ruthenium/pharmacology , Ruthenium/chemistry , HEK293 Cells , Coordination Complexes/pharmacology , Coordination Complexes/metabolism , Antineoplastic Agents/chemistryABSTRACT
Fluorene-based low molar weight derivatives were synthesized in Suzuki reactions by using key starting materials 9-benzylidene-2,7-dibromofluorene or 3-(2,7-dibromofluoren-9-ylmethylen)-9-ethylcarbazole and various aryl boronic acids. Photophysical properties of the compounds were investigated in different solutions as well as in solid state. The thermal investigations showed that the obtained compounds are highly thermally stable with temperatures of 5% mass loss (T5%) in the range of 311-432 °C. Some of the compounds also exhibited very high glass transition temperatures exceeding 125 °C. The presented molecules were electrochemically active and showed the energy band gap below 2.97 eV. The investigations were supported by DFT calculations and the photovoltaic ability of the presented compounds was tested in the organic-inorganic solar cells.