Manavathu EK, Alangaden GJ, Vashishtha SC, Dimmock JR; Interscience Conference on Antimicrobial Agents and Chemotherapy.

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 1996 Sep 15-18; 132 (abstract no. F184).

Wayne State University, Detroit, MI.

Previous studies in our laboratories have revealed that a number of Mannich bases of styryl ketones have antimicrobial properties. Therefore, four members of a new class of conjugated styryl ketones (designated NC1175, NC1213, NC1215 and NC1216) were examined for their ability to inhibit microbial growth. NC1175 at low concentrations inhibited the growth of a variety of yeasts and filamentous fungi pathogenic to man (MICs ranged from 0.19 micromolar to 6.25 micromolar and MFCs were only two-fold higher). The fungicidal effect of NC1175 was rapid, and concentration-dependent. Repeated freezing and thawing of the stock solution, and incubation at 37 degrees Celsius for 6 hr failed to diminish the bioactivity of the compound. The inhibitory effect was not removable by washing the cells with and resuspending them in drug-free medium. Dose-response studies including sub-MIC concentrations showed that complete inhibition of C. albicans growth was achieved only at concentrations equal to or greater than the MIC. Pregrowth of C. albicans cells in the presence of subinhibitory concentrations of NC1175 did not affect the MIC values of the compound. Cytotoxic studies of NC1175 using a variety of normal and neoplastic human cells revealed that the average IC(50) value was 25.64 micromolar, approximately 4- to 135-fold higher than the MIC values obtained for various fungi. Although conjugated styryl ketones have the ability to react with free and protein-associated thiols, the mode(s) of action of these compounds in fungi is not understood. These data prompt further investigation of the antifungal properties of this class of compounds, and suggest that modification of NC1175 may yield compound(s) even more highly active against pathogenic fungi.

Publication Types:

• Meeting Abstracts

Keywords:

• Antifungal Agents
• Fungi
• Humans
• Ketones
• Male
• Microbial Sensitivity Tests
• NC 1175
• Piperidines
• classification

Other ID:

• 98927703

UI: 102234877

From Meeting Abstracts