title: Synthesis of novel 1,2,5-trisubstituted benzimidazoles as potential antitumor agents.
abstract: Novel methyl 1-(5-tert-butyl-1H-pyrazol-3-yl)-2-(aryl)-1H-benzo[d]imidazole-5-carboxylates 11 were synthesized by following a four-step strategy involving a nucleophilic aromatic displacement (S(N)Ar) and a solvent free approach as key steps for the formation of the desired products. Structure of intermediates and products were confirmed by X-ray diffraction as well as the tautomeric rearrangement suffered by the pyrazole moiety during the curse of the final cyclization process. Several of the obtained compounds were screened by the US National Cancer Institute (NCI) for their ability to inhibit 60 different human tumor cell lines. Products 11b and 11n exhibited the highest activity against a range of cancer cell lines with remarkable values in panels of Non-Small Cell Lung Cancer, Melanoma and Leukemia, with GI(50) range of 1.15-7.33 μM and 0.167-7.59 μM, respectively, and suitable LC(50) with values greater than 100 μM.
authors: Grupo de Investigación de Compuestos Heterocíclicos, Departamento de Química, Universidad del Valle, AA 25360 Cali, Colombia. rodrigo.abonia@correounivalle.edu.co
authors: Rodrigo
authors: R
authors: Abonia
authors: Edwar
authors: E
authors: Cortés
authors: Braulio
authors: B
authors: Insuasty
authors: Jairo
authors: J
authors: Quiroga
authors: Manuel
authors: M
authors: Nogueras
authors: Justo
authors: J
authors: Cobo
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D003500:Cyclization; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D021241:Spectrometry, Mass, Electrospray Ionization; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000970:Antineoplastic Agents; D001562:Benzimidazoles