The development of resistance to current antifungal therapeutics drives the search for effective new agents. The fact that some acetophenone-derived Mannich bases had shown antifungal activities in our previous studies led us to design and synthesize acetophenone-derived bis Mannich bases, B1-B5, bis(b b-aroylethyl)methylamine hydrochlorides, to evaluate their antifungal activity. These bis Mannich bases were then converted to the corresponding piperidinols, C1-C5, which are structural isomers of bis derivatives, 3-aroyl-4-aryl-1-methyl-4-piperidinol hydrochlorides, to see alterations in biological activity. A stability study of B1 and C1 was also carried out to estimate whether they alkylate the thiols. All compounds studied have shown antifungal activity, especially against dermatophytes (Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans, and Microsporum canis), in the concentration range studied (2-128 m mg/ml). The activity was especially apparent against T. tonsurans. All compounds had at least equal antifungal activity compared with the reference compound amphotericin-B against T. tonsurans. Bis Mannich bases were generally found to be more potent compounds than their structural isomer piperidinols. The results of our stability studies suggest that thiol alkylation may contribute to the antifungal activity of the Mannich bases synthesized. Even though all compounds showed antifungal activity against dermatophytes, bis Mannich bases B1, B2, B4, and B5 appear to have potential for developing novel antifungal agents against dermatophytes.
Enzyme-linked immunosorbent assay (ELISA) was adapted to measure antibodies against Aspergillus fumigatus, Thermoactinomyces vulgaris and Micropolyspora faeni. Mycelial and culture fluid antigens were used separately to analyze antibodies in three study groups: farmer's lung patients, patients with bronchitis and healthy control persons. The mycelial antigen of A. fumigatus gave more positive results than the corresponding culture fluid antigen. The situation was reversed for the actinomycetes. For this reason either a mycelial antigen or a combination of mycelial and culture fluid antigens should be used in ELISA in routine tests. The prevalence and the titers of antibodies against the three microbes detected by ELISA were higher in the farmer's lung group than in the other two groups.
The development of resistance to current antifungal therapeutics drives search for new effective agents. Some Mannich bases have antifungal activity, but no information is available regarding the antifungal activity of acetophenone derived Mannich bases. Mono Mannich bases of acetophenone 1-3 were synthesized and converted into their corresponding bis derivatives, 5-7. Representative quaternary derivatives 4 and 8 were also synthesized. Antifungal activities of the compounds were evaluated using some yeasts and dermatophytes in vitro. Mono Mannich base 3 and quaternary compounds 4 and 8 were found to be 2-16 times more potent than the reference compound amphotericin B against dermatophytes: Trichophyton rubrum, Trichophyton mentagrophytes, and Microsporum canis. Compounds 4 and 8 were also found to be 2 times more effective compared with amphotericin B against the yeast Saccharomyces cerevisiae. Quaternization procedure improved the biological activity dramatically, whereas conversion of mono Mannich bases to corresponding bis derivatives generally did not affect antifungal activity. Our results suggest that acetophenone derived mono Mannich base 3 and quaternary derivatives 4 and 8 may serve as leading compounds for further studies to develop new antifungal agents with their highly potent antifungal activity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.