863413-99-4Relevant academic research and scientific papers
Open saccharin-based secondary sulfonamides as potent and selective inhibitors of cancer-related carbonic anhydrase IX and XII isoforms
D'ascenzio, Melissa,Guglielmi, Paolo,Secci, Daniela,Carradori, Simone,Florio, Rosalba,Mollica, Adriano,Ceruso, Mariangela,Supuran, Claudiu T.,Akdemir, Atilla,Sobolev, Anatoly P.
, p. 51 - 59 (2017/11/08)
A large number of novel secondary sulfonamides based on the open saccharin scaffold were synthesized and evaluated as selective inhibitors of four different isoforms of human carbonic anhydrase (hCA I, II, IX and XII, EC 4.2.1.1). They were obtained by re
Design, synthesis and evaluation of N-substituted saccharin derivatives as selective inhibitors of tumor-associated carbonic anhydrase XII
D'Ascenzio, Melissa,Carradori, Simone,De Monte, Celeste,Secci, Daniela,Ceruso, Mariangela,Supuran, Claudiu T.
, p. 1821 - 1831 (2014/03/21)
A series of N-alkylated saccharin derivatives were synthesized and tested for the inhibition of four different isoforms of human carbonic anhydrase (CA, EC 4. 2.1.1): the transmembrane tumor-associated CA IX and XII, and the cytosolic CA I and II. Most of the reported derivatives inhibited CA XII in the nanomolar/low micromolar range, hCA IX with KIs ranging between 11 and 390 nM, whereas they were inactive against both CA I (KIs >50 μM) and II (KIs ranging between 39.1 nM and 50 μM). Since CA I and II are off-targets of antitumor carbonic anhydrase inhibitors (CAIs), the obtained results represent an encouraging achievement for the development of new anticancer candidates without the common side effects of non-selective CAIs. Moreover, the lack of an explicit zinc binding function on these inhibitors opens the way towards the exploration of novel mechanisms of inhibition that could explain the high selectivity of these compounds for the inhibition of the transmembrane, tumor-associated isoforms over the cytosolic ones.
Novel Spirosuccinimides with Incorporated Isoindolone and Benzisothiazole 1,1-Dioxide Moieties as Aldose Reductase Inhibitors and Antihyperglycemic Agents
Wrobel, Jay,Dietrich, Arlene,Woolson, Shiela A.,Millen, Jane,McCaleb, Michael,et al.
, p. 4613 - 4627 (2007/10/02)
Compounds from two novel series of spirosuccinimides were prepared.Analogs of series 2 possessed a spiro-fused isoindolone moiety while those of series 3 contained a spiro-fused benzisothiazole S,S-dioxide group.These compounds were evaluated as aldose reductase inhibitors (ARI) in vitro by their ability to inhibit glyceraldehyde reduction using a partially purified bovine lens aldose reductase preparation and in vivo as inhibitors of galactitol accumulation in the lens, sciatic nerve, and diaphragm of galactose-fed rats.Many members from the isoindolone series 2,particularly those containing an isoindolone N-methyl moiety, showed good in vitro and in vivo potency.The most potent member, the 6-chloro analog 32, was resolved, and aldose reductase activity was found to reside almost exclusively in the (+)-enantiomer.Compound 32 was approximately equipotent in the sciatic nerve of the galactose-fed rat to other cyclic imide ARI's of similar in vitro activity, namely sorbinil and ADN-138 and also to tolrestat, an acetic acid-based ARI (ED50's 4-8 mg/kg).Compounds from both series, 2 and 3, were also found to lower plasma glucose levels of genetically obese db/db and ob/ob mice with potency similar to that of ciglitazone.However, members from these series failed to lower insulin levels of the ob/ob mouse at the doses tested.
