Issue 12, 2018

Novel O-methyl goniofufurone and 7-epi-goniofufurone derivatives: synthesis, in vitro cytotoxicity and SAR analysis

Abstract

Novel goniofufurone (1) and 7-epi-goniofufurone (2) derivatives bearing a methoxy group at the C-5 and/or C-7 positions were prepared and their in vitro antitumour activity against some human tumour cell lines was evaluated. Some of the analogues displayed powerful antiproliferative effects against the studied tumour cells, but almost all of them were non-cytotoxic toward the normal cells (MRC-5). A SAR study reveals that the introduction of a methoxy group at the C-7 position may increase the antiproliferative effects of the analogues. The most active compounds are 7-O-methyl derivatives of goniofufurone (3) and 7-epi-(+)-goniofufurone (6), which exhibited 1177- and 451-fold higher potencies than the leads 1 and 2 toward the MDA-MB 231 cell line. At the same time, compound 3 is almost 1.5-fold more active than the commercial drug doxorubicin (DOX) against the same cell line. Flow cytometry data confirmed that the cytotoxic effects of these analogues are mediated by apoptosis, additionally revealing that these molecules induced changes in the K562 cell cycle distribution.

Graphical abstract: Novel O-methyl goniofufurone and 7-epi-goniofufurone derivatives: synthesis, in vitro cytotoxicity and SAR analysis

Supplementary files

Article information

Article type
Research Article
Submitted
29 Aug 2018
Accepted
22 Oct 2018
First published
26 Oct 2018

Med. Chem. Commun., 2018,9, 2017-2027

Novel O-methyl goniofufurone and 7-epi-goniofufurone derivatives: synthesis, in vitro cytotoxicity and SAR analysis

J. Francuz, M. Popsavin, S. Djokić, V. Kojić, T. Srdić-Rajić, M. V. Rodić, D. Jakimov and V. Popsavin, Med. Chem. Commun., 2018, 9, 2017 DOI: 10.1039/C8MD00431E

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