1024172-89-1Relevant academic research and scientific papers
Conjugates of degraded and oxidized hydroxyethyl starch and sulfonylureas: Synthesis, characterization, and in vivo antidiabetic activity
Abbas, Muhammad Azhar,Hameed, Shahid,Farman, Muhammad,Kressler, J?rg,Mahmood, Nasir
, p. 120 - 127 (2015/01/30)
Orally administered drugs usually face the problem of low water solubility, low permeability, and less retention in bloodstream leading to unsatisfactory pharmacokinetic pro file of drugs. Polymer conjugation has attracted increasing interest in the pharmaceutical industry for delivering such low molecular weight (Mw) drugs as well as some complex compounds. In the present work, degraded and oxidized hydroxyethyl starch (HES), a highly biocompatible semisynthetic biopolymer, was used as a drug carrier to overcome the solubility and permeability problems. The HES was coupled with synthesized N-arylsulfonylbenzimidazolones, a class of sulfonylurea derivatives, by creating an amide linkage between the two species. The coupled products were characterized using GPC, FT-IR, 1H NMR, and 13C NMR spectroscopy. The experiments established the viability of covalent coupling between the biopolymer and N-arylsulfonylbenzimidazolones. The coupled products were screened for their in vivo antidiabetic potential on male albino rats. The coupling of sulfonylurea derivatives with HES resulted in a marked increase of the hypoglycemic activity of all the compounds. 2,3-Dihydro-3-(4-nitrobenzensulfonyl)-2-oxo-1H-benzimidazole coupled to HES10100 was found most potent with a 67% reduction in blood glucose level of the rats as compared to 41% reduction produced by tolbutamide and 38% by metformin. (Chemical Equation Presented).
Identification and development of novel inhibitors of toxoplasma gondii enoyl reductase
Tipparaju, Suresh K.,Muench, Stephen P.,Mui, Ernest J.,Ruzheinikov, Sergey N.,Lu, Jeffrey Z.,Hutson, Samuel L.,Kirisits, Michael J.,Prigge, Sean T.,Roberts, Craig W.,Henriquez, Fiona L.,Kozikowski, Alan P.,Rice, David W.,McLeod, Rima L.
experimental part, p. 6287 - 6300 (2010/12/25)
Toxoplasmosis causes significant morbidity and mortality, and yet available medicines are limited by toxicities and hypersensitivity. Because improved medicines are needed urgently, rational approaches were used to identify novel lead compounds effective against Toxoplasma gondii enoyl reductase (TgENR), a type II fatty acid synthase enzyme essential in parasites but not present in animals. Fifty-three compounds, including three classes that inhibit ENRs, were tested. Six compounds have antiparasite MIC90s ≤ 6 μM without toxicity to host cells, three compounds have IC90s A?. The crystal structure reveals that the aliphatic side chain of compound 19 occupies, as predicted, space made available by replacement of a bulky hydrophobic residue in homologous bacterial ENRs by Ala in TgENR. This provides a paradigm, conceptual foundation, reagents, and lead compounds for future rational development and discovery of improved inhibitors of T. gondii.
