Antifungal Evaluation of Bis Mannich Bases Derived from Acetophenones and Their Corresponding Piperidinols and Stability Studies

• Published in: Biological & pharmaceutical bulletin 2002, Vol.25(10), pp.1307-1310
• Main Authors: Gul, Halise Inci, Ojanen, Tarja, Hänninen, Osmo
• Format: Article
• Language: English
• Subjects: acetophenone; Acetophenones - chemistry; Acetophenones - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; antifungal activity; Antifungal agents; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Arthrodermataceae - drug effects; Arthrodermataceae - growth & development; Biological and medical sciences; dermatophyte; Drug Evaluation, Preclinical - methods; Drug Stability; mannich base; Mannich Bases - chemistry; Mannich Bases - pharmacology; Medical sciences; Microbial Sensitivity Tests - statistics & numerical data; Pharmacology. Drug treatments; Piperidones - chemistry; Piperidones - pharmacology; Yeasts - drug effects; Yeasts - growth & development
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.25.1307

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(β-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 μg/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.