Adamantane-linked 1,2,4-triazoles: Crystal structures, in vitro antimicrobial and anti-proliferative activities, and molecular docking analysis
摘要
The reaction of 5-(adamantan-1-yl)-4-butyl-2,4-dihydro-3H-1,2,4-triazole-3-thione 5 with 1-substituted piperazines, N-methylaniline or N-benzylaniline, and formaldehyde solution in ethanol at room temperature yielded the corresponding 2-aminomethyl derivatives 6a-c, 7a and 7b in good yields. 3-(Adamantan-1-yl)-5-(arylmethylthio)-4H-1,2,4-triazol-4-amines 10a-f were prepared via reaction of 5-(adamantan-1-yl)-4-amino-4H-1,2,4-triazole-3-thiol 9 with various benzyl or substituted benzyl halides in DMF, in the presence of anhydrous potassium carbonate. The structures of the synthesized compounds were characterized by elemental analysis, 1H NMR, 13C NMR and by X-ray crystallography. The in vitro antimicrobial activity of compounds 6a-c, 7a, 7b and 10a-f was assessed against a panel of standard pathogenic bacterial and fungal strains. The synthesized compounds were also evaluated for in vitro anti-proliferative activity against five human tumor cell lines. Molecular docking analysis of the most active compounds with SphK1 kinase revealed that extensive hydrophobic interactions between the ligands and active site residues may be responsible for the observed activity. Both the adamantane cage and the butyl moiety were involved in these hydrophobic interactions with the active site residues.