28831-29-0Relevant academic research and scientific papers
Design and synthesis of new benzylidene-quinazolinone hybrids as potential anti-diabetic agents: In vitro α-glucosidase inhibition, and docking studies
Ayyad, Rezk R.,Ibrahim, Albaraa,Khalifa, Mohamed M.,Mansour, Ahmed M.,Sakr, Helmy M.
, (2021/11/08)
A novel series of benzylidene-quinazolinone hybrids 8a,b and 10a-n were designed, synthesized, and evaluated for their in vitro α-glucosidase inhibitory effect aiming to discover efficient anti-diabetic agents. The synthesized compounds were assessed for their in vivo anti-hyperglycemic activities against STZ-induced hyperglycemic rats. Five compounds (10m, 10f, 10c, 10d and 8b) demonstrated potent activities with percent reduction in blood glucose levels of 43.07, 40.14, 39.83, 37.04 and 36.16, respectively. The most active members were further evaluated in vitro for their α-glucosidase inhibitory binding affinities. Among them, Compound 10m containing 4-hydroxybenzylidene moiety and compound 10f with 4-chlorobenzylidene moiety connected to the acetohydrazide demonstrated the most potent inhibitory activities towards α-glucosidase with IC50 values of 561 and 610 μM, respectively. Molecular docking study was performed in order to understand the molecular interactions between the molecule and enzyme.
Molecular modeling studies and synthesis of novel methyl 2-(2-(4-Oxo-3-aryl-3,4-dihydroquinazolin-2-ylthio)acetamido)alkanoates with potential anti-cancer activity as inhibitors for methionine synthase
Elfekki, Ismail Mahmoud,Hassan, Walid Fathalla Mohamed,Elshihawy, Hosam Eldin Abd Elhamed,Ali, Ibrahim Ahmed Ibrahim,Eltamany, Elsayed Hussein Mostafa
, p. 675 - 694 (2014/08/05)
Cobalamin-dependant cytosolic enzyme methionine synthase (MetS) catalyses the transfer of a methyl group from the methyltetrahydrofolate (MTHF) to homocysteine (Hcy) to produce methionine and tetrahydrofolate (THF). MetS is over-expressed in the cytosol of certain breast and prostate tumour cells. Methionine used as a source of one carbon atom for the building of the DNA of the tumour cells, structural protein and enzymes. In this study, we designed, synthesized and evaluated the cytotoxic activity of a series of substituted methyl 2-(2-(4-oxo-3-aryl-3,4-dihydroquinazolin-2-ylthio)acetamido)acetate and dipeptide that mimic the substructure of MTHF. These inhibitors were docked in to the MTHF binding domain in such the same way as MTHF in its binding domain. The free energies of the binding were calculated and compared to the IC 50 values. This series has been developed by dicyclohexylcarbodiimide (DCC) and azide coupling methods of amino acid esters with carboxylic acid derivatives, respectively. Compound methyl 3-hydroxy-2-(2-(3-(4-methoxyphenyl)- 4-oxo-3,4-dihydroquinazolin-2-ylthio)acetamido)propanoate exhibited the highest IC50 value 20 μg/mL against PC-3 cell line and scored the lowest free energy of the binding (-07.19 kJ/mol).
