Adamantane-Isothiourea Hybrid Derivatives: Synthesis Characterization In Vitro Antimicrobial and In Vivo Hypoglycemic Activities

摘要

A new series of adamantane-isothiourea hybrid derivatives, namely 4-arylmethyl (Z)-N′-(adamantan-1-yl)-morpholine-4-carbothioimidates >7a–>e and 4-arylmethyl (Z)-N′-(adamantan-1-yl)-4-phenylpiperazine-1-carbothioimidates >8a–>e were prepared via the reaction of N-(adamantan-1-yl)morpholine-4-carbothioamide >5 and N-(adamantan-1-yl)-4-phenylpiperazine-1-carbothioamide >6 with benzyl or substituted benzyl bromides, in acetone, in the presence of anhydrous potassium carbonate. The structures of the synthesized compounds were confirmed by ¹H-NMR, ¹³C-NMR, electrospray ionization mass spectral (ESI-MS) data, and X-ray crystallographic data. The in vitro antimicrobial activity of the new compounds was determined against certain standard strains of pathogenic bacteria and the yeast-like pathogenic fungus Candida albicans. Compounds >7b, >7d and >7e displayed potent broad-spectrum antibacterial activity, while compounds >7a, >7c, >8b, >8d and >8e were active against the tested Gram-positive bacteria. The in vivo oral hypoglycemic activity of the new compounds was carried on streptozotocin (STZ)-induced diabetic rats. Compounds >7a, >8ab, and >8b produced potent dose-independent reduction of serum glucose levels, compared to the potent hypoglycemic drug gliclazide.