Synthesis of new dithiolethione and methanethiosulfonate systems endowed with pharmaceutical interest

Abstract

Here we report synthetic methodology affording in the most efficient way the rapid preparation of new dithiolethiones (DTTs) and methanethiosulfonates (MTSs). These were evaluated as STAT3 inhibitors since these electrophilic systems could react with thiol groups of STAT3-SH2 domain. The results showed that MTSs strongly interacted with the SH2 domain, whereas the corresponding DTTs possessed lower affinity, independently from the nature of the linked heterocyclic scaffold.

New Acyl Derivatives of 3-Aminofurazanes and Their Antiplasmodial Activities

“…The resonance of the amino protons was shifted 0.5 ppm downfield. The desired compound 1 was finally obtained by reaction of 9 with sodium hydride and 3-methylbenzoyl chloride in DMF ( Scheme 1 ) [ 28 ]. The successful amide bond formation was detected by a significant change in the NMR spectrum.…”

“…The amides 1 , 10 – 14 , 16 , 17 and 26 – 29 were obtained by coupling the amino furazan 9 with the respective benzoyl chlorides that were commercially available or generated by the reaction of benzoic acids and oxalyl dichloride ( Scheme 2 ) [ 28 , 29 ]. Reaction of the N -hydroxy succinimide ester of the 3-(trifluoromethoxy)benzoic acid with 9 yielded 15 [ 30 ].…”

Towards the Inhibition of Protein–Protein Interactions (PPIs) in STAT3: Insights into a New Class of Benzothiadiazole Derivatives

“…Furthermore, since several STAT3 inhibitors have been reported as irreversible cysteine binders (e.g., Stattic and S3I-201) [15][16][17][18], we decided to evaluate the activity of compound 1 versus the cysteine residues located around the STAT3-SH2 domain (Cys468, Cys542, Cys550, Cys687, and Cys712) and to shed light on its mechanism of interaction by MS, UV, LC, and NMR studies. a hot spot should compete with the original protein partner of the PPI, thus resulting in disruption of its function, the aim of our ongoing studies [8][9][10][11][12][13] is the identification of small molecules that are able to bind the Src homology 2 (SH2) domain of STAT3, preventing STAT3 dimerization and thus its activation. With this purpose, in the present work, some compound libraries were analyzed by means of a structure-based virtual screening performed on the STAT3-SH2 domain (see the Molecular Modeling section).…”

“…The large surface area of STAT3 and the chemistry of these interactions [6], which are very different from those of better-known targets such as enzymes and G-protein-coupled receptors, could represent significant hurdles, although a number of successful examples have demonstrated that it is possible to overcome them and develop PPI modulators [7]. Since the binding of a ligand to a hot spot should compete with the original protein partner of the PPI, thus resulting in disruption of its function, the aim of our ongoing studies [8][9][10][11][12][13] is the identification of small molecules that are able to bind the Src homology 2 (SH2) domain of STAT3, preventing STAT3 dimerization and thus its activation. With this purpose, in the present work, some compound libraries were analyzed by means of a structure-based virtual screening performed on the STAT3-SH2 domain (see the Molecular Modeling section).…”

Novel 3,3-disubstituted oxindole derivatives. Synthesis and evaluation of the anti-proliferative activity

“…Herein, based on our experience in the functionalization of oxindole derivatives [32][33][34] and in the transformation of heterocyclic rings, [35][36][37][38] we describe the synthesis of a new class of 3,3-disubstituted oxindoles, bearing a nitrogen substituent in C-3 exploiting a metal free pathway. Continuing our researches in the synthesis of anticancer compounds, [39][40][41][42][43][44][45][46][47][48][49] the aim was to investigate the potential biological activity of the target compounds on different cancer cell lines.…”