Synthesis, Antimicrobial, and Anti-Proliferative Activities of Novel 4-(Adamantan-1-yl)-1-arylidene-3-thiosemicarbazides, 4-Arylmethyl N′-(Adamantan-1-yl)piperidine-1-carbothioimidates, and Related Derivatives

Abstract

The reaction of 4-(adamantan-1-yl)-3-thiosemicarbazide 3 with various aromatic aldehydes yielded the corresponding thiosemicarbazones 4a–g. 1-Adamantyl isothiocyanate 2 was reacted with 1-methylpiperazine or piperidine to yield the corresponding N-(adamantan-1-yl)carbothioamides 5 and 6, respectively. The latter was reacted with benzyl or substituted benzyl bromides to yield the S-arylmethyl derivatives 7a–c. Attempted cyclization of 1,3-bis(adamantan-1-yl)thiourea 8 with chloroacetic acid via prolonged heating to the corresponding thiazolidin-4-one 9 resulted in desulfurization of 8 to yield its urea analogue 10. The thiazolidin-4-one 9 and its 5-arylidene derivatives 11a,b were obtained via microwave-assisted synthesis. The in vitro antimicrobial activity of the synthesized compounds was evaluated against a panel of Gram-positive and Gram-negative bacteria and yeast-like pathogenic fungus Candida albicans. Compounds 7a–c displayed marked broad spectrum antibacterial activities (minimal inhibitory concentration (MIC), 0.5–32 μg/mL) and compounds 4a and 4g showed good activity against Candida albicans. Nine representative compounds were evaluated for anti-proliferative activity towards three human tumor cell lines. Compounds 7a–c displayed significant generalized anti-proliferative activity against all the tested cell lines with IC50 < 10 μM.