An upcoming drug for onychomycosis: Tavaborole

Abstract

Fungal infection of the nail as well as nail bed is termed as ‘onychomycosis’. It is caused by dermatophytes, non-dermatophytic fungal species and yeasts like Candida albicans. It is traditionally treated by topical antifungals, systemic agents like ketoconazole, griseofulvin, itraconazole, fluconazole, etc. Chemical avulsion or surgical removal of nail can also be tried to treat this disease. In spite of all these treatment options available, podiatrists were always in search of an ideal drug molecule with lesser side effects and which may improve the patient compliance. This exhaustive search led to the discovery of a better antifungal agent, known as “Tavaborole.” A systematic literature search was carried out using databases such as PubMed, Cochrane Reviews, Google Scholar, etc. Detailed information about onychomycosis and tavaborole was gathered. Tavaborole is the first oxaborole antifungal agent approved by FDA in July 2014. It is marketed under the trade name “Kerydin.” It acts by inhibiting protein synthesis in the fungus. It inhibits an enzyme known as cytosolic leucyl-transfer RNA synthetase, or LeuRS, which plays a key role in fungal essential protein synthesis. Dermatitis at the site of topical application, erythema, exfoliation and ingrowing toe nail has been reported in 1% of subjects. Tavaborole may offer a promising role in the treatment of onychomycosis and may compell podiatrists to offer its use in onychomycosis. The present study describes about chemical nature, mechanism of action and two completed phase 3 clinical trial findings of Tavaborole.

Onychomycosis: a review

“…Tavaborole is an updated formulation of oxaborole, a boronbased drug that inhibits fungal protein synthesis at the point of cytosolic leucyl-transfer RNA synthetase. 135 It has broad-spectrum activity against dermatophytes, NDMs and yeasts. It penetrates the nail well due to its small size and hydrophilicity.…”

Acral manifestations of fungal infections

“…According to clinical trials, tavaborole topical solution 5% may be an alternative to other drugs that are applied topically. 27,46,49,50 Luliconazole, which is another promising drug in the treatment of onychomycosis, does not yet have sufficient clinical data and further trials are needed. 51 Nail plate excision and matricectomy are only rarely performed in selected cases.…”

Synthesis and antimicrobial properties of cyclic fluorodiamines containing boronate esters

“…Indeed, Velcade, or bortezomib, is used for the treatment of multiple myeloma (a cancer of the plasma cells) and mantle cell lymphoma (a cancer of the lymph nodes). After, not as this remarkable step forward in boron pharmaceutical chemistry, Tavaborole or Kerydin, ® (Figure B) a simple fluorine‐containing boron compound, has been marketed as a topical antifungal medication for the treatment of onychomycosis, a fungal infection of the nail and nail bed …”

“…After, not as this remarkable step forward in boron pharmaceutical chemistry, Tavaborole or Kerydin, ® ( Figure 1B) a simple fluorine-containing boron compound, has been marketed as a topical antifungal medication for the treatment of onychomycosis, a fungal infection of the nail and nail bed. [8] The bioactivity associated with small-molecule boron compounds is believed to arise from the electrophilic nature of the three-coordinate boron atom, which contains an essentially empty formally p-derived orbital. The boron atom can readily form dative Lewis acid-base bonds with nucleophiles (ie, the hydroxyl group in serine) and transform from a neutral trigonal three-coordinate species into a four-coordinate tetrahedral adduct.…”