Spiro[pyrrolidine-3, 3´-oxindole] as potent anti-breast cancer compounds: Their design, synthesis, biological evaluation and cellular target identification
نویسندگان
چکیده
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.
منابع مشابه
Design, Synthesis and Biological Evaluation of4-(Imidazolylmethyl)-2-(4-methylsulfonyl phenyl)-Quinoline Derivatives as Selective COX-2 Inhibitors and In-vitro Anti-breast Cancer Agents
A new group of 4-(Imidazolylmethyl) quinoline derivatives possessing a methylsulfonyl COX-2 pharmacophore at the para position of the C-2 phenyl ring were designed and synthesized as selective COX-2 inhibitors and in-vitro anti breast cancer agents. In-vitro COX-1 and COX-2 inhibition studies showed that all the compounds were potent and selective inhibitors of the COX-2 isozyme with IC50 value...
متن کاملDesign, Synthesis and Biological Evaluation of4-(Imidazolylmethyl)-2-(4-methylsulfonyl phenyl)-Quinoline Derivatives as Selective COX-2 Inhibitors and In-vitro Anti-breast Cancer Agents
A new group of 4-(Imidazolylmethyl) quinoline derivatives possessing a methylsulfonyl COX-2 pharmacophore at the para position of the C-2 phenyl ring were designed and synthesized as selective COX-2 inhibitors and in-vitro anti breast cancer agents. In-vitro COX-1 and COX-2 inhibition studies showed that all the compounds were potent and selective inhibitors of the COX-2 isozyme with IC50 value...
متن کاملFacile, regio- and diastereoselective synthesis of spiro-pyrrolidine and pyrrolizine derivatives and evaluation of their antiproliferative activities.
A number of novel spiro-pyrrolidines/pyrrolizines derivatives were synthesized through [3+2]-cycloaddition of azomethine ylides with 3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones 2a-n. Azomethine ylides were generated in situ from the reaction of 1H-indole-2,3-dione (isatin, 3) with N-methylglycine (sarcosine), phenylglycine, or proline. All compounds (50 μM) were evaluated for their...
متن کاملA Facile One-Pot Construction of Succinimide-Fused Spiro[Pyrrolidine-2,3'-Oxindoles] via 1,3-Dipolar Cycloaddition Involving 3-Amino Oxindoles and Maleimides.
Increasing interests have been invested in the development of synthetic strategies toward the construction of spiro[pyrrolidine-2,3'-oxindole], which is the core structural skeleton in some compounds with diverse biological activities. In this work, an efficient diastereoselective 1,3-dipolar cycloaddition reaction of azomethine ylides generated in situ from 3-amino oxindoles and aldehydes with...
متن کاملDesign, synthesis and biological evaluation of Ciprofloxacin- peptide conjugates as anticancer agents
Cancer has emerged as a leading cause of death throughout the world. Peptides are a novel class of anticancer agents that can specifically target cancer cells with low toxicity to normal tissues and thus, offer new opportunities for future cancer treatment. On the other hand, Ciprofloxacin, an antibiotic, also known to its anticancer property for enabling cell cycle arrest and creating double s...
متن کامل