Biological Characterization of the Antimicrobial Activity of Arasertaconazole Nitrate

N. MARTI, C. TARRAGO, D. PALOP, M. DELGADO-JIMENEZ, A. GUGLIETTA;

Author address: 

Res. and Dev. Ctr.. Ferrer Internacional SA, Barcelona, Spain.

Abstract: 

Background: Sertaconazole nitrate, a topical antimycotic agent, consists of an equimolar mixture of the 2 enantiomers, R-(-)-sertaconazole (arasertaconazole) and S-(+)-sertaconazole. The enantiomers were synthesized and their antifungal, antibacterial, anti-inflammatory activities and the affinity for the target of the enantiomer were assessed. Methods: Antifungal and antibacterial activities:A total of 157 strains including yeasts (42), dermatophytes (17), filamentous fungi (11), Malassezia spp. strains (11) and bacterial strains (S.aureus (10), S.epidermidis (10), S.pyogenes (10), E.faecalis (10), Corynebacterium sp. (10), S.agalactiae (11), B.fragilis (9) and P.acnes (6) strains were used to score antifungal and antibacterial activities using CLSI methods. Anti-inflammatory activity: The anti-inflammatory activity was evaluated in a mouse ear oedema model of irritant dermatitis and was expressed as % of inhibition of the inflammation related to the control group. Mechanism of action: The mechanism of action was assessed using IC50 determination of ergosterol synthesis in C.albicans culture. Results: We found that, in addition to the very potent in vitro activity against yeasts, dermatophytes and opportunistic fungi, arasertaconazole nitrate also proved active against microorganisms involved in secondary bacterial infection. Arasertaconazole nitrate displayed a moderate anti-inflammatory activity, suggesting that it may provide further clinical benefit. Arasertaconazole inhibits ergosterol synthesis with an IC50 inhibition value of 0.5 x 10 -7M. Conclusions: Arasertaconazole nitrate has demonstrated a strong in vitro activity against clinically relevant fungal and bacterial species. Clinical development of arasertaconazole is currently underway.
2009

abstract No: 

M-350

Full conference title: 

49th Annual ICAAC
    • ICAAC 49th