2. Academic Validation
  3. Synthesis and biological screening for cytotoxic activity of N-substituted indolines and morpholines

Synthesis and biological screening for cytotoxic activity of N-substituted indolines and morpholines

  • Eur J Med Chem. 2016 Sep 14:120:296-303. doi: 10.1016/j.ejmech.2016.05.024.
Phuong Doan 1,  Anzhelika Karjalainen 1,  Jerome G Chandraseelan 1,  Ossi Sandberg 1,  Olli Yli-Harja 2,  Tomi Rosholm 3,  Robert Franzen 3,  Nuno R Candeias 4,  Meenakshisundaram Kandhavelu 5
Affiliations

Affiliations

  • 1 Molecular Signaling Lab, Computational Systems Biology Research Group, Department of Signal Processing, Tampere University of Technology, P.O. Box 553, 33101 Tampere, Finland.
  • 2 Molecular Signaling Lab, Computational Systems Biology Research Group, Department of Signal Processing, Tampere University of Technology, P.O. Box 553, 33101 Tampere, Finland; Institute for Systems Biology, 1441N 34th Street, Seattle, WA 98103-8904, USA.
  • 3 Department of Chemistry and Bioengineering, Tampere University of Technology, P.O. Box 553, 33101 Tampere, Finland.
  • 4 Department of Chemistry and Bioengineering, Tampere University of Technology, P.O. Box 553, 33101 Tampere, Finland. Electronic address: [email protected].
  • 5 Molecular Signaling Lab, Computational Systems Biology Research Group, Department of Signal Processing, Tampere University of Technology, P.O. Box 553, 33101 Tampere, Finland. Electronic address: [email protected].
PMID: 27214140 DOI: 10.1016/j.ejmech.2016.05.024
Abstract

Development of novel Anticancer drugs is inevitable to improve treatment of cancers. In this study, novel derivatives of indoline and morpholine were synthesized and tested for their cytotoxic effects on osteosarcoma and Human Embryonic Kidney cells. To characterize cytotoxicity and the mechanism of cell death, we used cytotoxicity, migration, Apoptosis markers and mitochondrial calcium assays. Among the compounds tested, the indoline derivatives, generally, produced a higher cytotoxic effect compared to the morpholine derivatives, in osteosarcoma cells. Specifically, new indoline derivative N-(2-hydroxy-5-nitrophenyl(4'-methylphenyl)methyl)indoline exhibited effective cytotoxic activity, with an IC50 of ∼74 μM. The same molecule induced cell death by Apoptosis and inhibited migration of the cells. Further, analysis of mitochondrial calcium levels revealed the existence of calcium dependent cell death mechanisms in different cell types. Therefore, N-(2-hydroxy-5-nitrophenyl(4'-methylphenyl)methyl)indoline can be considered as a potential drug-lead compound towards the discovery of new anti-cancer agents.

Keywords

Anticancer; Apoptosis induction; Cytotoxicity; Indoline; Morpholine.

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