Synthesis, antimicrobial and anti-inflammatory activities of novel 5-(1-adamantyl)-1,3,4-thiadiazole derivatives

Abstract New 1-adamanyl-1,3,4-thiadiazole derivatives namely, 5-(1-adamantyl)-1,3,4-thiadiazoline-2-thione 3 , 5-(1-adamantyl)-3-(benzyl- or 4-substituted benzyl)-1,3,4-thiadiazoline-2-thione 4a–d , 5-(1-adamantyl)-3-(4-substituted-1-piperazinylmethyl)-1,3,4-thiadiazoline-2-thiones 5a–c , 2-[5-(1-adamantyl)-2-thioxo-1,3,4-thiadiazolin-3-yl]acetic acid 7 , (±)-2-[5-(1-adamantyl)-2-thioxo-1,3,4-thiadiazolin-3-yl]propionic acid 9 , 3-[5-(1-adamantyl)-2-thioxo-1,3,4-thiadiazolin-3-yl]propionic acid 11 , N -[5-(1-adamantyl)-1,3,4-thiadiazol-2-yl]- N ′-arylthioureas 15a–c and 5-(1-adamantyl)-1,3,4-thiadiazoline-2-one 16 , were synthesized and tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans . Compounds 7 , 9 , 15b and 15c displayed marked activity against the tested Gram-positive bacteria, while compound 3 was highly active against the tested Gram-negative bacteria. Compounds 4b , 7 and 15c were weakly or moderately active against C. albicans . In addition, the in vivo anti-inflammatory activity of the synthesized compounds was determined using the carrageenan-induced paw oedema method in rats. The propionic acid derivative 9 produced good dose-dependent anti-inflammatory activity.