NOVEL ANTI-FUNGAL AGENTS AS CLASSICAL ISOSTERES OF MICONAZOLE AND ECONAZOLE

Ronald Bartzatt*

ABSTRACT

Fungal infections can be invasive and life threatening. Considering their substantial causation of morbidity and even mortality, the fact that only a limited number of therapeutic agents are available must be remedied. This study presents the consideration of five classical isosteres each of miconazole and econazole. Formation of classical isosteres of drugs is long established and successful approach to enhance the phamaceutical efficacy and increase the population of successful medicaments. Isosteres presented here utilize -CH3, -NH2, -OH, -Br, or -SH, to substitute the halogen atom (-Cl) on both miconazole and econazole. The molecular properties for all isosteres are presented and compared to the parent drugs miconazole and econazole. Analysis by non-metric multidimensional scaling clearly showed the distinction of the isosteres when compared to the parent drugs miconazole and econazole, by molecular properties. Neighbor joining cluster analysis indicated that the -SH isostere is most similar to the parent drug, for both miconazole and econazole. Both miconazole and econazole showed one violation of the Rule of 5, this violation being the Log P value for both. Interestingly, at least three isosteres for both parent drugs showed zero violations of the Rule of 5, indicating improved absorption and permeation compared to the parent drugs.

Keywords: econazole, miconazole, anti-fungal, isosteres.