Inactivation of the glutamine/amino acid transporter ASCT2 by 1,2,3-dithiazoles: proteoliposomes as a tool to gain insights in the molecular mechanism of action and of antitumor activity

Prognostic significance of amino-acid transporter expression (LAT1, ASCT2, and xCT) in surgically resected tongue cancer

“…An experimental study has described that the inhibition of ASCT2 reduces the availability of glutamine and other amino acids transported by ASCT2, and this could inhibit the survival of cancer cells depending on increased glutamine metabolism (Oppedisano et al , 2012). Therefore, ASCT2 could be the potential target for anticancer therapeutics as well.…”

Ring transformations of 2-hydroxy-(4-chloro-5 H -1,2,3-dithiazol-5-ylideneamino)arenes

“…27 Direct displacement of the dithiazoles C4 chlorine atom has proved to be difficult, 17a and the intramolecular cyclisation of the (dithiazolylideneamino)phenol 5a to afford the benzoxazine 6a is a very rare example of a cyclisation onto the dithiazole C4 position that maintains the integrity of the dithiazole ring. The only other known example is the reaction of 5-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione (10) with secondary alkylamines to yield 6-carbamoyl-5-oxo-5H-furo [2,3-d] [1,2,3] dithiazoles (11) (Scheme 4). 28 However, this cyclisation proceeds via an ANRORC style mechanism where the amine attacks the ring sulfur to generate a disulfide intermediate that then recyclises.…”

“…Early reports on the biological activity of [(4-chloro-5H-1,2,3-dithiazol-5-ylidene)amino]arenes showed that some 1,2,3-dithiazoles have antifungal 6 and herbicidal 7 activities, while more recently, interesting antitumour, 8 antibacterial 9 activities and inactivation of the glutamine/amino acid transporter ASCT2 10 have been demonstrated. Furthermore, benzo and heteroazine fused 1,2,3-dithiazoles are of interest to the material sciences.…”

The Conversion of 5,5′-Bi(1,2,3-dithiazolylidenes) into Isothiazolo[5,4-d]isothiazoles

“…At this stage, it is not possible to give an accurate mechanism, as several possibilities exist. Previous studies, nevertheless, reveal the dithiazole S2 atom to be marginally more susceptible to thiophilic attack [49], and based on this we propose the ring opening of both dithiazoles to generate the dianion 17 that then collapses to the 14 π 4,8-disubstituted [1–3]dithiazino[6,5- e ][1,2,3]dithiazine 18 which collapses to the thermodynamically more stable 10 π 3,6-disubstituted isothiazolo-[5,4- d ]isothiazole 8 (Scheme 5). Attempts to treat 3,6-diphenylisothiazolo[5,4- d ]isothiazole 8b with elemental sulfur or active sulfur (DABCO/S 8 ) [50] led to no reaction supporting that the reaction was not in equilibrium and the product was not convertible back to the starting dithiazole 11b .…”