Abstract
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.
Highlights
The adamantane nucleus was recognized early as an essential pharmacophore in various pharmacologically-active drugs
In view of the diverse pharmacological properties of adamantane and isothiourea derivatives, and following our previous studies on the chemical and biological properties of adamantane and following our previous studies on the chemical and biological properties of adamantane derivatives [10,30,31,32,33], we report the synthesis and characterization of novel adamantane derivatives [10,30,31,32,33], we report the synthesis and characterization of novel adamantane derivatives containing an isothiourea moiety as potential antimicrobial and/or hypoglycemic agents
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
Summary
The adamantane nucleus was recognized early as an essential pharmacophore in various pharmacologically-active drugs. Amantadine, the first adamantane-based drug, was approved for the treatment of Influenza A infection [3,4,5] and as an anti-Parkinsonian drug [6]. Further studies based on amantadine resulted in the development of the potent antiviral drugs rimantadine [7] and tromantadine [8]. Numerous adamantane-based analogues were proved to possess significant inhibitory activity against human immunodeficiency viruses (HIV) [9,10,11,12]. The synthetic retinoid derivative CD437 was developed as a potent inducer of apoptosis in human head and neck squamous cell carcinoma [13]. Potent bactericidal and fungicidal activities were reported for several
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