1395312-82-9

Upstream product

• 6723-30-4 O-2-tetrahydro-2H-pyranhydroxylamine 
• 207910-90-5 3-(3-bromophenyl)-2-oxopropanoic acid 
• 906722-01-8 (4E)-4-[(3-bromophenyl)methylidene]-2-methyl-4,5-dihydro-1,3-oxazol-5-one 
• 1181696-34-3 C₁₀H₉BrO₃ 
• 1395312-74-9 (E)-methyl 3-(3-bromophenyl)-2-(tetrahydro-2H-pyran-2-yloxyimino)propanoate 

Downstream Products

• 1395312-90-9 (2E,2'E)-N,N'-(2,2'-disulfanediylbis(ethane-2,1-diyl))bis(3-(3-bromophenyl)-2-(tetrahydro-2H-pyran-2-yloxyimino)propanamide) 

Relevant academic research and scientific papers

Carbonic Anhydrase XII Inhibitors Overcome Temozolomide Resistance in Glioblastoma

The natural product primary sulfonamide, psammaplin C (1), when used in combination with clinically used chemotherapeutic drugs, including temozolomide, reverses multidrug resistance and increases survival in glioblastoma, a highly aggressive primary brain tumor. We showed previously that the mechanism of action of 1 is novel, acting to indirectly interfere with P-glycoprotein drug efflux activity as a consequence of carbonic anhydrase XII (CA XII) inhibition. To build structure-activity relationships, 45 derivatives of 1 were designed, synthesized, and evaluated against a panel of CA isoforms. Compound 55 was identified as a potent inhibitor of CA XII (Ki = 0.56 nM) and was investigated in vitro and in vivo using samples from glioblastoma patients. The results strengthen the possibility that co-therapy of temozolomide with a CA XII inhibitor may more effectively treat glioblastoma by suppressing an important temozolomide resistance mechanism.

CARBONIC ANHYDRASE INHIBITORS

Compounds are provided which are inhibitors of the CAXII enzyme. Due to the interaction between CAXII and Pgp, such compounds may be useful in lowering the chemoresistance of a cancer allowing for co-administration with existing anti-cancer agents.

Fluorescent analogs of the marine natural product psammaplin A: Synthesis and biological activity

The symmetrical disulfide psammaplin A from the marine sponge Pseudoceratina sp. was synthesized and structurally altered by replacement of one of the α-(hydroxyimino)acyl units by a fluorescent 4-coumarinacetyl moiety. Thus, the first fluorescent analogs of psammaplin A were obtained. Structural variation also covered the substitution pattern of the phenyl ring. Cytotoxicity of psammaplin A against the mouse fibroblast cell line L-929 (IC50 0.42 μg mL-1) was about two-fold higher than that of the fluorescent hybrid compounds, whereas the disulfide containing two 4-coumarinacetyl moieties was inactive. Fluorescence microscopy revealed uptake of the 4-coumarinacetyl-α-(hydroxyimino)acyl hybrids into the cytoplasm leading to fluorescence in close proximity of the nuclear envelope, most likely in the Golgi apparatus. We did not observe strong fluorescence inside the nucleus, where most of the target histone deacetylases are located. We conclude that reduction of the disulfide probably takes place outside the nucleus. The psammaplin-derived thiol exhibited potent activity against histone deacetylase in the low nanomolar range, but diminished cytotoxicity. Antimicrobial activity of the new derivatives was also determined.