Novel 20(S)-sulfonylamidine derivatives of camptothecin and the use thereof as a potent antitumor agent: A patent evaluation of WO2015048365 (A1)

Giovanni Luca Beretta, Nadia Zaffaroni, Greta Varchi

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

A series of camptothecin (CPT) derivatives featuring acyl-esterification of the 20(S)-hydroxyl group with a residue containing a sulfonylamidine moiety is synthesized via a Cu catalyzed three-component reaction. The compounds show remarkable cytotoxicity against a panel of tumor cells, including a cell line exhibiting Multi-Drug Resistant (MDR) phenotype. The patent develops 9a, the best derivative of the series, that i) selectively poisons DNA Topoisomerase I (TopoI); ii) induces cell-cycle S-phase arrest with activation of the DNA damage response pathway and apoptosis induction and iii) shows considerable in vivo antitumor potency. We envision that the peculiar modification of the 20(S)-hydroxyl group of CPT with a sulfonylamidine residue will play a continuing role in affording new TopoI poison drug candidates for therapeutic applications.

Original languageEnglish (US)
Pages (from-to)637-642
Number of pages6
JournalExpert Opinion on Therapeutic Patents
Volume26
Issue number5
DOIs
StatePublished - May 3 2016

Keywords

  • Camptothecins
  • Copper catalysis
  • DNA Topoisomerase I
  • Drug resistance
  • Lactone ringopening
  • Sulfonylamidine

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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