title: 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. [Formula: see text].
authors.affiliation: a Department of Pharmaceutical Sciences , Università degli Studi di Milano , Milano , Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Gabriele
authors.affiliation: b Department of Pharmacological and Biomolecular Sciences , Università degli Studi di Milano , Milano , Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Ricci
authors.affiliation: a Department of Pharmaceutical Sciences , Università degli Studi di Milano , Milano , Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Meneghetti
authors.affiliation: c Department of Pharmaceutical and Pharmacological Sciences , Università degli Studi di Padova , Padova , Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Ferri
authors.affiliation: d Center for Drug Discovery, Graduate School of Pharmaceutical Sciences , University of Shizuoka , Shizuoka , Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Asai
authors.affiliation: a Department of Pharmaceutical Sciences , Università degli Studi di Milano , Milano , Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Sparatore
mesh_terms: D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D006801:Humans; D008024:Ligands; D008698:Mesylates / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D018909:src Homology Domains
chemical_list: D008024:Ligands; D008698:Mesylates; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C074502:methanethiosulfonate
keywords: Anticancer drug; S3I-201 analogs; SH2 antagonist; STAT3; cytotoxicity