Anticancer and structure-activity relationship evaluation of 3-(naphthalen-2-yl)-N,5-diphenyl-pyrazoline-1-carbothioamide analogs of chalcone |
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Institution: | 1. Department of Chemistry, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India;2. Department of Physics, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India;3. Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576 104, Karnataka, India;4. Department of Atomic and Molecular Physics, MIT Campus, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India;5. Department of Studies in Physics, Manasagangotri, University of Mysore, Mysuru 570006, India;6. School of Physics, University of Hyderabad, Hyderabad 500046, India |
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Abstract: | To identify new potent chemotherapeutic agents, we synthesized compounds with 3-(naphthalen-2-yl)-N,5-diphenyl-pyrazoline-1-carbothioamide (NDPC) skeletons and evaluated their cytotoxicities using a clonogenic long-term survival assay. Their half-maximal cell growth inhibitory concentrations ranged from a few hundred nanomolars to a few micromolars. Further biological experiments including flow cytometry and western blotting analysis were performed with the derivative showing the best cytotoxicity. To identify a target protein of the selected compound, an in vitro kinase assay was carried out, which revealed that aurora kinases A and B were inhibited by the test compound, and this was confirmed using western blot analysis. The molecular binding mode between the selected compound and the kinases was elucidated using in silico docking. The structural conditions required for good cytotoxicity were identified based on the quantitative relationships between the physicochemical properties of the derivatives and their cytotoxicities. |
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Keywords: | Colorectal Clonogenicity QSAR Flow cytometry Immunofluorescence microscopy |
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