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Sci Rep. 2016 Aug 30;6:32213. doi: 10.1038/srep32213.

Spiro[pyrrolidine-3, 3´-oxindole] as potent anti-breast cancer compounds: Their design, synthesis, biological evaluation and cellular target identification.

Author information

1
Department of Chemistry, School of Natural Sciences, Shiv Nadar University, Dadri, Chithera, Gautam Buddha Nagar, 201314, Uttar Pradesh, India.
2
Department of Life Sciences, School of Natural Sciences, Shiv Nadar University, Dadri, Chithera, Gautam Buddha Nagar, 201314, Uttar Pradesh, India.
3
Shantani Proteome Analytics Pvt. Ltd. 100 NCL Innovation Park, Dr. HomiBhabha Road, Pune - 411 008, India.

Abstract

The spiro[pyrrolidine-3, 3´-oxindole] moiety is present as a core in number of alkaloids with substantial biological activities. Here in we report design and synthesis of a library of compounds bearing spiro[pyrrolidine-3, 3´-oxindole] motifs that demonstrated exceptional inhibitory activity against the proliferation of MCF-7 breast cancer cells. The synthesis involved a one pot Pictet Spengler-Oxidative ring contraction of tryptamine to the desired scaffolds and occurred in 1:1 THF and water with catalytic trifluoroacetic acid and stoichiometric N-bromosuccinimide as an oxidant. Phenotypic profiling indicated that these molecules induce apoptotic cell death in MCF-7 cells. Target deconvolution with most potent compound 5l from the library, using chemical proteomics indicated histone deacetylase 2 (HDAC2) and prohibitin 2 as the potential cellular binding partners. Molecular docking of 5l with HDAC2 provided insights pertinent to putative binding interactions.

PMID:
27573798
PMCID:
PMC5004205
DOI:
10.1038/srep32213
[Indexed for MEDLINE]
Free PMC Article

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