Abstract
A synthetic strategy to access a novel family of nucleoside analogues bearing a C3'-nitrile substituted all-carbon quaternary center is presented herein. These purine bearing scaffolds were tested in two pancreatic cancer cell lines harboring either wild-type (BxPC3) or G12V KRAS (Capan2) mutations. A promising compound was shown to have significantly greater efficacy in the Capan2 cell line as compared to Gemcitabine, the clinical gold standard used to treat pancreatic cancer.
Keywords:
Capan2; KRAS mutation; Nucleoside analogues; Pancreatic cancer; Stereogenic quaternary center.
Copyright © 2020 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amides / chemistry
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Antineoplastic Agents / chemistry*
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Antineoplastic Agents / pharmacology
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Apoptosis / drug effects
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Benzylamines / chemistry
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Cell Proliferation / drug effects
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Deoxycytidine / analogs & derivatives*
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Deoxycytidine / chemistry
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Deoxycytidine / pharmacology
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Dose-Response Relationship, Drug
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Drug Screening Assays, Antitumor
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Gemcitabine
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Glycosylation
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Humans
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Mutation
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Nitriles / chemistry*
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Pancreatic Neoplasms / drug therapy*
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Phosphoric Acids / chemistry
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Proto-Oncogene Proteins p21(ras) / genetics
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Purines / chemistry
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Structure-Activity Relationship
Substances
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Amides
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Antineoplastic Agents
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Benzylamines
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KRAS protein, human
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Nitriles
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Phosphoric Acids
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Purines
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Deoxycytidine
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phosphoramidic acid
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benzylamine
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Proto-Oncogene Proteins p21(ras)
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purine
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Gemcitabine