title: Structural and molecular docking studies of 4-benzyl-3-[(1-methylpyrrol- 2-yl)methyl]-4,5-dihydro-1H-1,2,4-triazol-5-one with anticancer activity.
abstract: The 1,2,4-triazoles are an important group of medicinal substances which exhibit a wide range of activity, such as analgesic, antibacterial, fungicidal, antinflammatory, antiviral and anticancer. As a part of our long-term study on 1,2,4- triazoles we synthesize 4-benzyl-3-[(1-methylpyrrol-2-yl)methyl]-4,5-dihydro-1H-1,2,4-triazol-5-one which is characterized with anticancer activity. Here, we present an exhaustive studies of its electronic and molecular structure, aimed to rationalize the observed pharmacological activity, supported by the molecular docking to the EGFR kinase domain ATP binding site. The structural studies include X-ray analysis, experimental and computed spectral analysis (1H and 13C NMR, IR) as well as conformational analysis and the frontal molecular orbitals (FMO) analysis. The results of molecular docking indicate that interaction of 4-benzyl-3-[(1-methylpyrrol-2-yl)methyl]-4,5-dihydro-1H-1,2,4-triazol-5-one with the EGFR kinase domain ATP binding site may be responsible for the observed anticancer activity of this 1,2,4-triazole derivative. Moreover, we find that formation of the respective ligand-protein complex is conditioned by the keto-enol tautomerism of the ligand, i.e. the energetic prevalence of the keto form.
authors: Department of Synthesis and Chemical Technology of Pharmaceutical Substances, Medical University of Lublin, Lublin, Poland. agnieszka.kaczor@umlub.pl
authors: Agnieszka A
authors: AA
authors: Kaczor
authors: Monika
authors: M
authors: Pitucha
authors: Zbigniew
authors: Z
authors: Karczmarzyk
authors: Waldemar
authors: W
authors: Wysocki
authors: Jolanta
authors: J
authors: Rzymowska
authors: Dariusz
authors: D
authors: Matosiuk
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D002460:Cell Line; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D005260:Female; D006801:Humans; D007536:Isomerism; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010051:Ovarian Neoplasms / Q000188:drug therapy; D011758:Pyrroles / Q000737:chemistry* / Q000494:pharmacology; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: C112392:4,5-dihydro-1H-1,2,4-triazol-5-one; C583372:4-benzyl-3-((1-methylpyrrol-2-yl)methyl)-4,5-dihydro-1H-1,2,4-triazol-5-one; D000970:Antineoplastic Agents; D011758:Pyrroles; D014230:Triazoles; C045575:1,2,4-triazole