21304-38-1Relevant articles and documents
Synthesis and Biological Evaluation of Novel 2-Aryl Benzimidazoles as Chemotherapeutic Agents
Morais, Goreti Ribeiro,Palma, Elisa,Marques, Fernanda,Gano, Lurdes,Oliveira, Maria Cristina,Abrunhosa, Antero,Miranda, Hugo Vicente,Outeiro, Tiago F.,Santos, Isabel,Paulo, Antonio
, p. 255 - 267 (2017/02/03)
Here, we describe the synthesis and preliminary biological evaluation of novel N-unsubstituted and N-methylated 2-aryl benzimidazole derivatives that contain fluorinated or hydroxylated alkyl substituents in the 4-N-aryl position and different substitution patterns (H vs Br vs I) in the benzimidazole ring. For the selected compounds and for comparison purposes, the congener benzothiazoles were also tested. The cytotoxic effect of 11 benzazole derivatives was evaluated in a panel of human cancer cell lines, such as breast (MCF7), melanoma (A375), cervix (HeLa), and glioblastoma (U87). In general, the compounds exerted a moderate cytotoxic activity against all cells tested. In particular, for the A375 and HeLa cells, the N-unsubstituted benzimidazoles 2 and 3 displayed a better cytotoxic profile than the respective N-methylated benzimidazole congeners (5 and 7). The biodistribution of compound 2, which has shown the highest cytotoxic activity active in the U87 glioblastoma cells (IC50= 45.2 ± 13.0), was evaluated in CD1 mice using its18F-labeled counterpart ([18F]2). These studies showed that compound 2 can cross the blood brain barrier with a reasonable brain uptake (1.24 and 2.81%I.A./g at 5 and 60 min p.i., respectively), which is a crucial issue for systemic chemotherapy of glioblastoma. Altogether, the in vitro antitumoral activity of benzimidazole 2 against the U87 cells and the ability of its18F-congener to cross the blood brain barrier provide a strong rationale to consider the reported fluoroalkylated 2-aryl benzimidazoles as lead candidates for the generation of chemotherapeutic agents, in particular, against highly aggressive brain tumors such as glioblastoma.
Exploring the Strength of the H-Bond in Synthetic Models for Heme Proteins: The Importance of the N?H Acidity of the Distal Base
Alberti, Mariza N.,Polyhach, Yevhen,Tzirakis, Manolis D.,T?dtli, Laura,Jeschke, Gunnar,Diederich, Fran?ois
supporting information, p. 10194 - 10202 (2016/07/19)
The distal hydrogen bond (H-bond) in dioxygen-binding proteins is crucial for the discrimination of O2with respect to CO or NO. We report the preparation and characterization of a series of ZnIIporphyrins, with one of three meso-phenyl rings bearing both an alkyl-tethered proximal imidazole ligand and a heterocyclic distal H-bond donor connected by a rigid acetylene spacer. Previously, we had validated the corresponding CoIIcomplexes as synthetic model systems for dioxygen-binding heme proteins and demonstrated the structural requirements for proper distal H-bonding to CoII-bound dioxygen. Here, we systematically vary the H-bond donor ability of the distal heterocycles, as predicted based on pKavalues. The H-bond in the dioxygen adducts of the CoIIporphyrins was directly measured by Q-band Davies-ENDOR spectroscopy. It was shown that the strength of the hyperfine coupling between the dioxygen radical and the distal H-atom increases with enhanced acidity of the H-bond donor.
Synthesis and biological evaluation of 5-substituted derivatives of benzimidazole
Vasic, Vesna P.,Penjisevic, Jelena Z.,Novakovic, Irena T.,Sukalovic, Vladimir V.,Andric, Deana B.,Kostic-Rajacic, Sladana V.
, p. 277 - 282 (2014/04/17)
A series of eight novel 5-substituted derivatives of benzimidazole was synthesized by condensation of the corresponding diamine with ethyl 4-[4- -(2-chlorophenyl)piperazin-1-yl]butanoate in refluxing 4 M hydrochloric acid. In vitro antibacterial activity against ten strains, namely Bacillus subtilis, Clostridium sporogenes, Streptosporangium longisporum, Micrococcus flavus, Sarcina lutea, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella enteritidis and Proteus vulgaris and antifungal activity against two fungal strains, namely Candida albicans and Saccharomyces cerevisiae, were evaluated. Of all the compounds screened for activity, 2-{3-[4-(2-chlorophenyl) piperazin-1-yl]propyl}-5-iodo-1H-benzimidazole and 2-{3-[4-(2-chlorophenyl) piperazin-1-yl]propyl}-5-methyl-1H-benzimidazole were associated with higher antifungal activity than commercial drugs.
