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

Expert Opinion on Therapeutic Patents
G L BerettaGreta Varchi

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.

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Citations

Oct 19, 2016·PLoS Neglected Tropical Diseases·Mark D MathewDonald Moerman
Nov 2, 2019·Current Topics in Medicinal Chemistry·Izabel Almeida AlvesMairim Russo Serafini
Sep 15, 2020·Expert Opinion on Therapeutic Patents·Hazem AhmedSimon M Ametamey
Jun 28, 2021·European Journal of Medicinal Chemistry·Noura KhaiwaTaleb H Al-Tel

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