Methanethiosulfonate derivatives as ligands of the STAT3-SH2 domain

Abstract

With the aim to discover new STAT3 direct inhibitors, potentially useful as anticancer agents, a set of methanethiosulfonate drug hybrids were synthesized. The in vitro tests showed that all the thiosulfonic compounds were able to strongly and selectively bind STAT3-SH2 domain, whereas the parent drugs were completely devoid of this ability. In addition, some of them showed a moderate antiproliferative activity on HCT-116 cancer cell line. These results suggest that methanethiosulfonate moiety can be considered a useful scaffold in the preparation of new direct STAT3 inhibitors. Interestingly, an unusual kind of organo-sulfur derivative, endowed with valuable antiproliferative activity, was occasionally isolated.

Keywords:

• Anticancer drug
• cytotoxicity
• SH2 antagonist
• STAT3
• S3I-201 analogs

Acknowledgements

The authors acknowledge the Italian Ministero dell’Università e della Ricerca (MIUR), under the National Interest Research Projects framework (PRIN 20105YY2HL) for the financial support.

Disclosure statement

Prof. A. Sparatore is a coauthor of two patent applications describing two molecules studied in the manuscript. However these two patents have been abandoned several years ago and therefore she has no conflicts of interest to disclose.