4479-70-3Relevant articles and documents
Design, synthesis, molecular modeling and anti-hyperglycemic evaluation of phthalimide-sulfonylurea hybrids as PPARγ and SUR agonists
El-Zahabi, Mohamed Ayman,Elbendary, Eman R.,Bamanie, Faida H.,Radwan, Mohamed F.,Ghareib, Salah A.,Eissa, Ibrahim H.
, (2019/07/16)
New series of phthalimide-sulfonylurea hybrids were prepared and examined for their in vivo anti-hyperglycemic activities in STZ-induced hyperglycemic rats using glibenclamide as a reference drug. Compounds 6c, 6d, 6g, 6h, 6j and 6k induced significant reduction in the blood glucose levels of diabetic rats ranging from 24.43 to 21.43%. Moreover, molecular docking and pharmacophore approaches were carried out to examine binding modes and fit values of the prepared compounds against PPARγ and SUR, respectively. Compounds 6c, 6d, 6j and 6m exhibited the highest binding free energies against PPARγ. Compounds 6c, 6j, 6k, 6l, and 6n showed the highest fit values against the generated pharmacophore model. Also, QSAR technique was carried out to estimate the proposed PPARγ binding affinities and insulin-secreting abilities. The synthesized compounds showed promising estimated activities. In-silico ADMET studies were performed to investigate pharmacokinetics of the synthesized compounds. They showed considerable human intestinal absorption with low BBB penetration.
Synthesis and molecular modelling studies of novel sulphonamide derivatives as dengue virus 2 protease inhibitors
Timiri, Ajay Kumar,Subasri, Selvarasu,Kesherwani, Manish,Vishwanathan, Vijayan,Sinha, Barij Nayan,Velmurugan, Devadasan,Jayaprakash, Venkatesan
, p. 74 - 82 (2015/08/11)
Abstract Development of antivirals for dengue is now based on rational approach targeting the enzymes involved in its life cycle. Among the targets available for inhibition of dengue virus, non-structural protein NS2B-NS3 protease is considered as a promising target for the development of anti-dengue agents. In the current study we have synthesized a series of 4-(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)benzene-1-sulphonamide derivatives and screened for DENV2 protease activity. Compounds 16 and 19 showed IC50 of DENV2 Protease activity with 48.2 and 121.9 μM respectively. Molecular docking and molecular dynamic simulation studies were carried out to know the binding mode responsible for the activity. MD simulations revealed that, NS2B/NS3 protease was more stable when it binds with the active compound. Structure optimization of the lead compounds 16 and 19 and their co-crystallization studies are underway.
Synthesis and evaluation of novel dapsone-thalidomide hybrids for the treatment of type 2 leprosy reactions
Yamasaki, Paulo Renato,Do Nascimento, Dejair Caetano,Chelucci, Rafael Consolin,De Faria Fernandes Belone, Andréa,Rosa, Patrícia Sammarco,Diório, Suzana Madeira,De Melo, Thais Regina Ferreira,Barbieri, Karina Pereira,Placeres, Marisa Campos Polési,Carlos, Iracilda Zepone,Chung, Man Chin,Dos Santos, Jean Leandro
, p. 3084 - 3087 (2014/06/24)
We synthesized a series of novel dapsone-thalidomide hybrids (3a-i) by molecular hybridization and evaluated their potential for the treatment of type 2 leprosy reactions. All of the compounds had analgesic properties. Compounds 3c and 3h were the most active antinociceptive compounds and reduced acetic acid-induced abdominal constrictions by 49.8% and 39.1%, respectively. The hybrid compounds also reduced tumor necrosis factor-α levels in lipopolysaccharide-stimulated L929 cells. Compound 3i was the most active compound; at concentrations of 15.62 and 125 μM, compound 3i decreased tumor necrosis factor-α levels by 86.33% and 87.80%, respectively. In nude mice infected with Mycobacterium leprae in vivo, compound 3i did not reduce the number of bacilli compared with controls. Compound 3i did not have mutagenic effects in Salmonella typhimurium strains TA100 and TA102, with or without metabolic activation (S9 mixture). Our results indicate that compound 3i is a novel lead compound for the treatment of type 2 leprosy reactions.
