Design, synthesis, antigiardial and in silico assessments of novel propargylamines containing nitroimidazole core. (8th October 2022)

• Record Type: Journal Article
• Authors: Behrouz, Somayeh; Soltani Rad, Mohammad Navid; Ganji, Zahra; Behrouz, Marzieh; Zarenezhad, Elham; Agholi, Mahmoud
• Is Part Of: Tetrahedron. Volume 124(2022)
• Publication Date: 2022-10-08
• Subjects: A3 coupling -- CDSCS -- Giardia lamblia -- Nitroimidazole -- Propargylamine -- Metronidazole; DENWVGQAKACUEF-UHFFFAOYSA-N -- ABPGTJHHMSKADZ-UHFFFAOYSA-N -- HOBCIJVZGGSZEK-UHFFFAOYSA-N -- YQBZUVLVUNTJNO-UHFFFAOYSA-N -- VJCYBTZNVFXPFA-UHFFFAOYSA-N -- JPGPJSYVHQLOCT-UHFFFAOYSA-N -- JGJMICVDTBWCIX-UHFFFAOYSA-N -- QNKGWJNBOUJPQI-UHFFFAOYSA-N -- YSWUNSYHGGQTST-UHFFFAOYSA-N -- GFYKASPFTJDUIC-UHFFFAOYSA-N -- CEOBKVHJKGDBMM-UHFFFAOYSA-N -- OIFIHNQEXHLMRO-UHFFFAOYSA-N -- ZDJCKZXEOZKNAH-UHFFFAOYSA-N -- YSOFXQPRTLECDD-UHFFFAOYSA-N -- UEARQXWFDSEBAB-UHFFFAOYSA-N; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2022.133007
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: Design, synthesis, antigiardial activity, and in silico pharmacokinetic and docking assessments of new propargylamine derivatives containing 2-methyl-5-nitroimidazole core are described. These propargylamines were efficiently synthesized through three-component reaction (A 3 coupling) between a preformed terminal alkyne (i.e.: 2-methyl-5-nitro-1-prop-2-ynyl-1 H -imidazole), different aromatic aldehydes, and cyclic amines in refluxing toluene catalyzed by copper-doped silica cuprous sulfate (CDSCS) as a reusable, environmentally benign and low-cost nanocatalyst. The antigiardial activity of the synthesized propargilamines was in vitro investigated against Giardia lamblia (G. lamblia) and compared with metronidazole (MTZ) as a selected reference drug. Among tested compounds, 4-(1-(4-chlorophenyl)-4-(2-methyl-5-nitro-1 H -imidazole-1-yl)but-2-ynyl)morpholine (2b ) displayed potent antigiardial activity even stronger than MTZ. The in silico physicochemical properties, pharmacokinetic profile, and drug likeness predictions were also carried out for all synthesized compounds and MTZ. Molecular docking study was also performed to predict the binding mode and interaction of 2b with triosephosphate isomerase enzyme. This study has determined the strong binding affinity of 2b to the active site of the enzyme. Graphical abstract: Image 1