HWN Suggests

New Antifungal Agents with Azole Moieties

Although challenging, the search for new antifungal agents increased in the last few years, due to the arise of resistance problems of fungi to the existing therapeutics, new fungal strains and... the increased occurrence of fungal infections in the past decades... Most used antifungal agents are included in the class of azoles. This family of compounds has shown over the decades a vast range of applications in the treatment of fungal infections and diseases, with increasing interest and use in the clinical setting. Therefore, the development of new promising molecules with an azole scaffold has rapidly emerged throughout the years.

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 Doctor Fungus

The azole antifungal agents inhibit the synthesis of ergosterol by blocking the action of 14-alpha-demethylase.

Articles of Interest

Antifungal Agents. Part II. The Azoles

Before 1978, amphotericin Band flucytosine were the only drugs available for the treatment of systemic fungal infections. The imidazoles, miconazole and ketoconazole, were introduced during the next 3 years. Intravenously administered miconazole served a limited therapeutic role and is no longer available. Orally administered ketoconazole, an inexpensive, effective, and convenient option for treating mucosal candidiasis, was widely used for a decade because it was the only available oral therapy for systemic fungal infections. During the 1990s, use of ketoconazole diminished because of the release of the triazoles fluconazole and itraconazole. Fluconazole is less toxic and has several pharmacologic advantages over ketoconazole, including penetration into the cerebrospinal fluid. In addition, it has superior efficacy against systemic candidiasis, cryptococcosis, and coccidioidomycosis. Despite a myriad of drug interactions and less favorable pharmacologic and toxicity profiles in comparison with fluconazole, itraconazole has become a valuable addition to the antifungal armamentarium.

Azole Antifungal Drug Toxicity—A Review

Azole antifungals helped by adding to therapeutic options in treatment of IFIs works by inhibiting 14α-lanosterol demethylase, a key enzyme in ergosterol biosynthesis, resulting in depletion of ergosterol and accumulation of toxic 14α-methylated sterols in membranes of susceptible fungus. Azoles are classified into two: the triazoles (fluconazole, itraconazole, voriconazole, posaconazole, and isavuconazole) and the imidazoles (ketoconazole). Despite wide spectrum activity, these drugs show toxic effects like hepatitis and inhibition of steroid hormone synthesis, prolonged corrected for heart rate (QTc) intervals...

Azole Antifungal Drugs: Old and New

The therapeutic armamentarium against both systemic and superficial fungal infections consists primarily of the polyenes, amphotericin B and nystatin; flucytosine, a fluorinated pyrimidine analogue; and the older antifungal azoles, clotrimazole, miconazole, and ketoconazole. Results of recent studies give promise that new investigational antifungal oral azole drugs, including itraconazole, fluconazole, and SCH 39304, will be exciting additions to current compounds.

Azole antifungals

Azole antifungals are a group of medicines that contain an azole ring and inhibit the growth of a wide range of fungi. They are classified into two groups: those with two nitrogens in the azole ring (the imidazoles; examples include clotrimazole, econazole, ketoconazole, miconazole, and tioconazole) and those with three nitrogens in the azole ring (the triazoles; examples include fluconazole, itraconazole, posaconazole, and voriconazole).

Azole antifungals

The practice of medicine has been transformed by the introduction by a series of antifungal azole agents starting with ketoconazole in 1985, but spurred on by fluconazole, itraconazole and voriconazole over the following 2 decades... Patient outcomes were transformed and oral therapy became possible. The low toxicity of these agents compared with amphotericin B was transformational.

Azole Fungicides and Their Endocrine Disrupting Properties

Azoles are antifungal agents used in both agriculture and medicine. They typically target the CYP51 enzyme in fungi and, by so doing, disrupt cell membrane integrity. However, azoles can also target various CYP enzymes in mammals, including humans, which can disrupt hormone synthesis and signaling. For instance, several azoles can inhibit enzymes of the steroidogenic pathway and disrupt steroid hormone biosynthesis. This is of particular concern during pregnancy, since sex hormones are integral to reproductive development. In other words, exposure to azole fungicides during fetal life can potentially lead to reproductive disease in the offspring.

Challenges in the Polyene- and Azole-Based Pharmacotherapy of Ocular Fungal Infections

Polyenes and azoles constitute 2 major drug classes in the antifungal armamentarium used to treat fungal infections of the eye such as fungal keratitis, endophthalmitis, conjunctivitis, and blepharitis. These classes of drugs have come to occupy an important niche in ophthalmic antifungal therapy due to their broad spectrum of activity against a variety of filamentous and yeast-like fungi.

Current and Emerging Azole Antifungal Agents

Major developments in research into the azole class of antifungal agents during the 1990s have provided expanded options for the treatment of many opportunistic and endemic fungal infections. Fluconazole and itraconazole have proved to be safer than both amphotericin B and ketoconazole. Despite these advances, serious fungal infections remain difficult to treat, and resistance to the available drugs is emerging.

Possible adverse events of imidazole antifungal drugs during treatment of vulvovaginal candidiasis...

Azole antifungal drugs are commonly used to treat vulvovaginal candidiasis (VVC). The nephrotoxicity and developmental toxicity of azole drugs have not been systematically analyzed in the real world.

Side effects of long-term azole therapy

Azole antifungals are the first-line of treatment or prophylaxis for many fungal infections. They are often administered long-term (weeks to months), which can be associated with a number of adverse effects.

“Azole menace”-An underappreciated trigger perpetuating the epidemic of antifungal therapeutic failure in cutaneous mycoses

The fastidious pharmacokinetic properties and related practical aspects of the triazole group of oral and topical antifungals, especially oral itraconazole seem to contribute significantly to the persistence of AFTF epidemic.