51759-60-5Relevant academic research and scientific papers
Synthesis of pyridinyl-benzo[d]imidazole/pyridinyl-benzo[d]thiazole derivatives and their yeast glucose uptake activity in vitro
Khan, Momin,Ahmad, Riaz,Rehman, Gauhar,Gul, Naeem,Shah, Sana,Salar, Uzma,Perveen, Shahnaz,Khan, Khalid Mohammed
, p. 984 - 993 (2019/10/28)
Background: Diabetes is the primary cause of fatality and disability all over the world, in recent past, we have reported various classes of compounds as anti-glycating agents and we have also reported benzimidazole and benzothiazole derivatives as a potential class of anti-glycating agents. This encouraged us to evaluate the pyridinyl benzimidazole/pyridinyl benzothiazole derivatives 1-27 for yeast glucose uptake activity. Methods: In the present study, an equimolar mixture of pyridine carboxaldehyde derivatives (1 mmol) and sodium metabisulphite (1 mmol) in DMF (10 mL) was stirred for 10 to 15 min, followed by addition of o-phenylene diamine/2-aminothiophenol (1 mmol) into it and refluxed for 3 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was poured into crushed ice. Precipitates were formed which were collected by filtration to produce compounds 1-27 in good yields. Recrystallization from methanol yielded pure crystals. Results: Our present study showed that all compounds showed a varying degree of yeast glucose uptake activity in the range IC50 = 36.43-272.20 μM, compared to standard metronidazole (IC50 = 41.86 ± 0.09 μM). Compounds 5 (IC50 = 38.14 ± 0.17 μM), 6 (IC50 = 40.23 ± 0.20 μM), and 7 (IC50 = 36.43 ± 0.02 μM) showed an excellent yeast glucose uptake activity better than the standard. Conclusion: Pyridinyl benzimidazole/pyridinyl benzothiazole derivatives 1-27 were synthesized, structurally characterized, and evaluated for in vitro yeast glucose uptake activity. Compounds 5 (IC50 = 38.14 ± 0.17 μM), 6 (IC50 = 40.23 ± 0.20 μM), and 7 (IC50 = 36.43 ± 0.02 μM) demonstrated potent yeast glucose uptake activity as compared to standard metronidazole (IC50 = 41.86 ± 0.09 μM). This study identified a number of potential lead molecules which can be helpful in lowering the blood glucose level in hyperglycemia.
Benzimidazole derivatives: Synthesis, leishmanicidal effectiveness, and molecular docking studies
Shaukat, Awais,Mirza, Hira M.,Ansari, Amna H.,Yasinzai, Masoom,Zaidi, Sohail Z.,Dilshad, Sana,Ansari, Farzana L.
, p. 3606 - 3620 (2013/07/26)
Leishmanolysin GP63 is a zinc metalloprotease, expressed at the surface of Leishmania promastigotes. Studies on this protein are hindered as only a limited number of effective non-toxic inhibitors of this drug target are known. Present study describes the identification of a variety of 2-aryl- and 5-nitro-2-arylbenzimidazoles as new GP63 inhibitors. All the compounds were tested for in vitro activity against the promastigote form of Leishmania major and showed very good activity. 2-(Thiophen-2-yl)-1H-benzimidazole (19) and 2-(1H-indol-3-yl)-5-nitro-1H-benzimidazole (34) with IC50 value of 0.62 μg/mL were identified as lead of this library. Molecular docking studies were performed on binding site of GP63 to study the binding mode of compounds. The results of both in vitro and in silico studies clearly indicated that benzimidazoles may serve as new drug candidates in the combat against leishmaniasis.
Metal-mediated inhibition of escherichia coli methionine aminopeptidase: Structure-activity relationships and development of a novel scoring function for metal-ligand interactions
Schiffmann, Rolf,Neugebauer, Alexander,Klein, Christian D.
, p. 511 - 522 (2007/10/03)
We report the discovery of thiabendazole as a potent inhibitor (K 1 = 0.4 μM) of Escherichia coli methionine aminopeptidase (ecMetAP) and the synthesis and pharmacological evaluation of thiabendazole congeners with activity in the upper nanomolar range, Elucidation of the X-ray structure of ecMetAP in complex with thiabendazole and an unrelated inhibitor that was independently described by another group showed that that both compounds bind to an additional CoII ion at the entrance of the active site. This unexpected finding explains the inactivity of the compounds under in vivo conditions. It also allows us to discuss the structure-activity relationships of this series of compounds in a meaningful way, based upon docking runs with an auxiliary metal ion, We describe a new scoring function for the evaluation of metal-mediated inhibitor binding that, unlike the previously used scoring function implemented in the docking program, allows us to distinguish between active and inactive compounds, Finally, conclusions for the structure-based design of in vivo-active inhibitors of ecMetAP are drawn.
Chemistry of 2-substituted benzimidazoles. 1. 5-Amino-2-methyl(aryl, arylalkyl, pyridyl)benzimidazoles
Ambacheu,Pleshakov,Baatkh,Zvolinskii,Kharlamova,Obynochnyi,Prostakov
, p. 421 - 428 (2007/10/03)
A series of 2-substituted benzimidazoles was synthesized. These products were consecutively converted into 5-nitro- and 5-amino-2-substituted benzimidazoles.
ACIDIC PROPERTIES OF BENZIMIDAZOLES AND SUBSTITUENT EFFECTS. V. PROTECTION OF BENZIMIDAZOLES BY N-ALKYL BOND FORMATION USING VINYLPYRIDINES
Ichikawa, Masataka,Yamamoto, Chiyuki,Hisano, Takuzo
, p. 3042 - 3047 (2007/10/02)
Vinylpyridines were utilized for protection of the benzimidazole N-H bond to give 1-(2-pyridylethyl)-benzimidazoles.The reaction was found to progress smoothly when glacial acetic acid was used as a catalyst.In the alkylation of 5- or 7-substituted-2-arylbenzimidazoles with vinylpyridines, the yield decreased with increasing electron-attracting effect of the substituent groups in the benzimidazole ring.On the other hand, the removal of pyridylethyl groups by the use of aluminum chloride as a catalyst was kinetically examined; a large excess of sodium hydroxide was used for decomposition of the intermediate adduct of aluminum chloride.The rate increased somewhat when electron-releasing substituent groups were present in the benzimidazole ring. 1--2-arylbenzimidazoles were resistant to removal of their (2-pyridyl)ethyl groups. 4-Vinylpyridine can be used more efficiently as a protecting agent.Keywords: 2-pyridylbenzimidazoles; protection with vinylpyridines for imidazole; 1-(2-pyridylethyl)-benzimidazoles; substituent effect on N-alkylation of benzimidazoles; rate of removal of pyridylethyl groups by aluminum chloride catalyst
