Open AccessSynthesis and Antiproliferative Activity of Nitric Oxide-Donor Largazole Prodrugs
Author(s) -
Matteo Borgini,
Claudio Zamperini,
Federica Poggialini,
Luca Ferrante,
Vincenzo Summa,
Maurizio Botta,
Romano Di Fabio
Publication year - 2020
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/acsmedchemlett.9b00643
Subject(s) - prodrug , nitric oxide , moiety , in vitro , chemistry , natural product , biochemistry , tumor cells , computational biology , pharmacology , combinatorial chemistry , biology , cancer research , stereochemistry , organic chemistry
The marine natural product Largazole is the most potent Class I HDAC inhibitor identified to date. Since its discovery, many research groups have been attracted by the structural complexity and the peculiar anticancer activity, due to its capability to discriminate between tumor cells and normal cells. Herein, we discuss the synthesis and the in vitro biological profile of hybrid analogues of Largazole, as dual HDAC inhibitor and nitric oxide (NO) donors, potentially useful as anticancer agents. In particular, the metabolic stability of the modified thioester moiety of Largazole, bearing the NO-donor function/s, the in vitro release of NO, and the antiproliferative activity in tumor cell lines are presented.