Function of the Econazole and its derivative

2018-09-21

Introduction 

Econazole, commonly used as sulfosalicylate and nitrate salt, is an imidazole broad-spectrum antifungal drug, which can not only interfere with the biosynthesis of fungal cell membrane, but also inhibit the synthesis of ribonucleic acid. Its nitrate salt is a white crystalline powder, extremely insoluble in water and slightly soluble in most organic solvents. Its mechanism of anti-bacterial property is the same as ketoconazole and the antibacterial spectrum is similar to miconazole. It shows strong antibacterial effect on Candida, Fonsecaea, Coccidioides, Histiocystis, Sporothrix and also shows antibacterial activities for Trichophyton spp, while exhibits weak antibacterial activity for the aspergillus, Sporotrichum schenckii and some of the Mucor. It has been widely utilized to treat fungal infections such as tinea corporis, tinea cruris, tinea pedis and chromophytosis, also used for treating candidiasis of the skin, vaginal candidiasis.

Pharmacologic action

Econazole sulfosalicylate is a dose-dependently drug, which shows inhibitory action for the fungus in low concentration and bactericidal action at high concentration. It can inhibit the biosynthesis of ergosterol or other sterols, which damages the cell membrane and changes the permeability of fungi to lead the leakage of important intracellular substances. Besides, it also shows inhibition for the biosynthesis of triglycerides and phospholipids of fungi, inhibiting the activities of oxidase and peroxidase, which leads the accumulation of hydrogen peroxide in cells thus resulting cell submicrostructure denaturation and cell necrosis. Especially, for the albicans Saccharomyces, the process of transforming a spore into an invasive hyphal form has also can be inhibited by Econazole.

Function

Econazole sulfosalicylate, an imidazole antifungal agent, is among the most frequently used topical formulations for the treatment of skin and mucosal infections, such as tinea cruris, tinea pedis and candida vaginitis, with a minimum inhibitory dose of 1 mol/m3. Its side effects such as irritation, redness, burning or itching have also been reported among 1–4% of patients. Furthermore, econazole significantly inhibits downstream target of the PI3K/AKT signaling pathway, the AKT phosphorylation, the expression of Bcl-2, and induced apoptosis in H661 and A549 cell lines, which suggest that the econazole is a promising PI3K inhibitor and a candidate anti-cancer drug for the treatment of lung cancer.

Pharmacokinetics and metabolism

The 3H marked econazole nitrate cream is applied to the normal and bruised skin of rabbits. The radiopharmaceutical determination test results show that the total amount of drug absorption is 6% and 10% in the first 7 hours, 21% and 30 in 48 hours respectively. The total absorption of radioactivity in the bruised skin is higher than regular skin. After the drug is absorbed by the skin, the plasma drug concentration reaches the peak (251 ng/ml) at 48 hours in normal skin and reaches the peak in 24 hours after skin scratch (270~321 ng/ml). The distribution of drug in normal and scraped skin tissues is similar after drug absorption. Detailedly, the concentration of drugs in liver, kidney, stomach and adrenal gland is the highest, followed by uterus, ovary and untreated skin. The absorbed drugs are excreted from urine and feces with same proportion.

References:

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4. Hughes T E T, Lodowski D T, Huynh K W, et al. Structural basis of TRPV5 channel inhibition by econazole revealed by cryo-EM[J]. Nature Structural & Molecular Biology, 2018, 25(1):53-60.

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