13570-08-6Relevant articles and documents
Design, synthesis, docking and QSAR study of substituted benzimidazole linked oxadiazole as cytotoxic agents, EGFR and erbB2 receptor inhibitors
Akhtar, Md Jawaid,Siddiqui, Anees Ahmad,Khan, Ahsan Ahmed,Ali, Zulphikar,Dewangan, Rikeshwer Prasad,Pasha, Santosh,Yar, M. Shahar
, p. 853 - 869 (2017)
The synthesis of benzimidazole linked oxadiazole derivatives designed as potential EGFR and erbB2 receptor inhibitors with anticancer and apoptotic activity were studied. Compounds 7a specifically inhibit EGFR and erbB2 receptor at 0.081 and 0.098 μM concentration. Some of the compounds showed strong, broad-spectrum antiproliferative activitiy when tested against five human cancer cell lines. Compounds 7a and 7n were more cytotoxic than 5-fluorouracil against MCF-7 cancer cell, with IC50values of 5.0 and 2.55 μM whereas, only 7a led to cell cycle arrest at G2/M phase accompanied by an increase in apoptosis. Compounds 7a and 7n showed normal architecture of myofibrils in cardiomyopathy study whereas only compound 7a showed nearly equal biochemical parameters (SGOT and SGPT) when compared to control. Molecular docking & 3D-QSAR studies were used to establish interactions of 7a and 7n within the active site of enzyme for ATP binding site of kinase domain.
General base catalyzed ester hydrolysis as a model of the ''charge relay'' system
Komiyama,Bender
, p. 13 - 20 (1977)
The validity of the 'charge relay' system in serine esterases was examined by use of the general base catalyzed hydrolysis of ethyl chloroacetate (I) as a model system. The general base catalytic rate for 2 benzimidazoleacetic acid (II) exhibited an eightfold positive deviation from the Bronsted plot including benzimidazole, imidazole, N methylimidazole (V), and acetate ion, though in nucleophilic catalysis of the hydrolysis of p nitrophenyl acetate, the point for II conformed to the Bronsted relationship together with imidazole and benzimidazole derivatives. The positive deviation of II from the Bronsted plot for the general base catalysis was attributed to the cooperativety of the carboxyl group of II, the imidazolyl group of II, and the hydroxyl group of water. The present result provides support for the 'charge relay' system. Furthermore, the (essentially) total loss of the enzymatic activity due to N 3 methylation of histidine 57 in α chymotrypsin is discussed in comparison to the general base catalysis of V in the hydrolysis of I, which is also favorable for the 'charge relay' system.
An efficient synthesis of novel di-heterocyclic benzazole derivatives and evaluation of their antiproliferative activities
Algul, Oztekin,Ersan, Ronak Haj,Alagoz, Mehmet Abdullah,Duran, Nizami,Burmaoglu, Serdar
, p. 6926 - 6938 (2020/08/13)
A series of unsymmetrical nine di-heterocyclic compounds of benzazole derivatives were synthesized at one step via cyclization reaction. The compounds evaluated for in?vitro cytotoxic activity against A549, A498, HeLa, and HepG2 cancer cell lines. The biological evaluation results show that 23, 26 and 29 exhibit better activity against HepG2 and HeLa cancer cell lines. Compound 23 also showed good activity against A549, and A498 cancer cell lines. The analogs were further performed molecular docking studies against human cytochrome P450 2C8 monooxygenase enzyme, calculated some theoretical quantum parameters, ADMET descriptor and molecular electrostatic potential analysis. The strategy applied in this research work may act as a perspective for the rational design of potential anticancer drugs. Communicated by Ramaswamy H. Sarma.
NOVEL FERROPORTIN INHIBITORS
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Page/Page column 243, (2017/05/10)
The invention relates to novel ferroportin inhibitors of the general formula (I) pharmaceutical compositions comprising them and the use thereof as medicaments, in particular for the prophylaxis and/or treatment of diseases caused by a lack of hepcidin or iron metabolism disorders, such as particularly iron overload states such as in particular thalassemia and hemochromatosis.
