Synthesis, Structural Studies and Molecular Modelling of a Novel Imidazoline Derivative with Antifungal Activity.
Six novel imidazoline derivatives were synthesized and tested in antifungal assays. One of the compounds, N-cyclohexyl-2-imino-3-(4-nitrophenyl)imidazolidine-1-carboxamide showed moderate activity against several clinical strains of Candida albicans. Its structure was solved by X-ray crystallography and its mode of action was deduced using molecular modelling. It was found to be similar to that of fluconazole. The potential for further optimization including SAR of the compound is briefly discussed.
Department of Synthesis and Chemical Technology of Pharmaceutical Substances, Medical University of Lublin, Chodzki 4a, 20-093 Lublin, Poland. tomasz.wrobel@umlub.pl.
Tomasz M
TM
Wróbel
Department of Pharmaceutical Microbiology, Medical University of Lublin, Chodzki 1, 20-093 Lublin, Poland. urszula.kosikowska@umlub.pl.
Urszula
U
Kosikowska
Department of Synthesis and Chemical Technology of Pharmaceutical Substances, Medical University of Lublin, Chodzki 4a, 20-093 Lublin, Poland. agnieszka.kaczor@umlub.pl.|School of Pharmacy, University of Eastern Finland, Yliopistonranta 1, P.O. Box 1627, FI-70211 Kuopio, Finland. agnieszka.kaczor@umlub.pl.
Agnieszka A
AA
Kaczor
Department of Pharmaceutical Microbiology, Medical University of Lublin, Chodzki 1, 20-093 Lublin, Poland. sylwia.andrzejczuk@umlub.pl.
Sylwia
S
Andrzejczuk
Department of Chemistry, Siedlce University of Natural Sciences and Humanities, 3 Maja 54, 08-110 Siedlce, Poland. kar@uph.edu.pl.
Zbigniew
Z
Karczmarzyk
Department of Chemistry, Siedlce University of Natural Sciences and Humanities, 3 Maja 54, 08-110 Siedlce, Poland. wwysocki@uph.edu.pl.
Waldemar
W
Wysocki
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warszawa, Poland.
Zofia
Z
Urbańczyk-Lipkowska
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warszawa, Poland. maja.morawiak@icho.edu.pl.
Maja
M
Morawiak
Department of Synthesis and Chemical Technology of Pharmaceutical Substances, Medical University of Lublin, Chodzki 4a, 20-093 Lublin, Poland. dariusz.matosiuk@umlub.pl.
Dariusz
D
Matosiuk
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D003022:Clotrimazole / Q000494:pharmacology; D006860:Hydrogen Bonding; D048288:Imidazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017953:Isocyanates / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation
D000935:Antifungal Agents; D048288:Imidazolines; D017953:Isocyanates; D003022:Clotrimazole
14-α-sterol demethylase; Candida albicans; X-ray analysis; antifungal; molecular modelling; synthesis