Behandlung von therapieresistenten Verrucae vulgares mit einem Ciclopirox-haltigen Lack

Szeimies, R.-M.; Wimmershoff, M. B.; Reisberger, Eva-Maria; Landthaler, Míchael

doi:10.1007/s001050100165

Cited by 3 publications

(2 citation statements)

References 13 publications

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“…We observed inhibition of DNA synthesis in a panel of cancer lines with IC 50 values ranging from 0.2 to 5 μM ( n = 8) and from 10 (HUVECs) to 25 (primary human lung fibroblasts) μM in nontransformed cells (data not shown). Other evidence suggesting antiproliferative activity of ciclopirox is found in its effect on warts 48. In a small pilot trial, 23 patients with common warts on their hands, feet or face that were resistant to conventional therapy were treated with an 8% ciclopirox lacquer once or twice daily.…”

Section: Discussionmentioning

confidence: 99%

The antifungal drug ciclopirox inhibits deoxyhypusine and proline hydroxylation, endothelial cell growth and angiogenesis in vitro

Clément

Hanauske-Abel

Wolff

et al. 2002

Intl Journal of Cancer

113

140

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The hypusine biosynthetic steps represent novel targets for intervention in cell proliferation. Hypusine is a rare amino acid, formed posttranslationally in one cellular protein, eIF5A, and is essential for cell proliferation. Deoxyhypusine hydroxylase, the metalloenzyme catalyzing the final step in hypusine biosynthesis, and prolyl 4-hydroxylase, a non-heme iron enzyme critical for collagen processing, can be inhibited by small chelating molecules that target their essential metal atom. We examined the effects of 5 compounds (ciclopirox, deferiprone, deferoxamine, mimosine and 2,2-dipyridyl) on these protein hydroxylases in HUVECs, on cell proliferation and on angiogenesis using 2 model assays: tube-like vessel formation on Matrigel and the chick aortic arch sprouting assay. These compounds inhibited cellular deoxyhypusine hydroxylase in a concentration-dependent manner, but their efficacy varied widely in the following order: ciclopirox3 deferoxamine32

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Section: Discussionmentioning

confidence: 99%

The antifungal drug ciclopirox inhibits deoxyhypusine and proline hydroxylation, endothelial cell growth and angiogenesis in vitro

Clément

Hanauske-Abel

Wolff

et al. 2002

Intl Journal of Cancer

113

140

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“…Since ciclopirox accumulates in the squamous layers of human skin and epithelia, achieving mM concentrations [146], it should be a suitable agent for the control of proliferative abnormalities in these layers. Ciclopirox causes remission of therapy-resistant human skin warts in vivo [91], and arrests the proliferation of malignant human cervical epithelial cells in vitro 2 . These findings make ciclopirox an excellent candidate for topical chemoprevention of intraepithelial neoplasias, in particular of the cervix, since a commercial preparation for treatment of fungal infections of the vagina is available.…”

Section: The Hag Dioxygenases : Emerging Targets For Therapeutic Intementioning

confidence: 99%

The HAG Mechanism: A Molecular Rationale For The Therapeutic Application Of Iron Chelators In Human Diseases Involving the 2-Oxoacid Utilizing Dioxygenases

Hanauske-Abel¹,

Popowicz²

2003

CMC

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'Iron chelation' is widely understood as synonymous with non-specificity and viewed as a purely physicochemical mode of action, without any defined biomolecular target, broadly interfering with metalloenzymes. The 2-oxoacid-utilizing dioxygenases challenge this preconception. A family of non-heme iron enzymes that rely on chelation-dependent catalysis, they employ common molecules like Krebs cycle intermediates as endogenous iron chelators and consume atmospheric oxygen, inserting one of its atoms into cellular components. These enzymes control the adaptation of cells to hypoxia; the reversal of mutagenic DNA alkylations, the initiation of DNA replication, the translation of mRNAs; the production of extracellular matrix proteins like collagens and fibrillins; and numerous metabolic pathways: from the synthesis of the gibberellin growth hormones of plants, and the formation of carnitine, atropine, endotoxins, and cephalosporin antibiotics, to the breakdown of amino acids. Their pivotal roles in human pathology encompass oncogenesis and cancer angiogenesis, scarring and organ fibrosis, inherited diseases, and retroviral infections. Their unique catalysis, termed earlier the 'HAG mechanism' and known in subatomic detail, requires at least three different substrates to form three different products, and proceeds as a ligand reaction at the non-heme iron atom inside the active site pocket, without any direct involvement of apoenzyme residues. The apoenzyme sterically controls ligand access to the metal. The HAG mechanism-based concept of catalytic chelation directed by an apoenzyme, not merely by complexation parameters, has enabled knowledge-guided design of systemic and tissue-selective inhibitors, and of clinical trials. The HAG mechanism also lends itself to the development of novel, man-made biocatalysts.

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Ciclopirox

Subissi

Monti

Togni

et al. 2010

Drugs

136

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Ciclopirox is a topical antimycotic agent belonging to the chemical class of hydroxypyridones and not related to azoles or any other class of antifungal agents. Its antimicrobial profile includes nearly all of the clinically relevant dermatophytes, yeasts and moulds, and is therefore broader than that of most other antimycotics. It is also active against certain frequently azole-resistant Candida species and against some bacteria. The mechanism of action of ciclopirox is different from that of other topical antifungal drugs, which generally act through ergosterol inhibition. The high affinity of ciclopirox for trivalent metal cations, resulting in inhibition of the metal-dependent enzymes that are responsible for the degradation of peroxides within the fungal cell, appears to be the major determinant of its antimicrobial activity. This unique and multilevel mechanism of action provides a very low potential for the development of resistance in pathogenic fungi, with cases of resistance rarely reported. Ciclopirox also displays mild anti-inflammatory effects in biochemical and pharmacological models; effects also shown in small clinical studies. Scavenging of reactive oxygen species released from inflammatory cells is a likely contributor to these anti-inflammatory effects. Ciclopirox, and its olamine salt, is available in multiple topical formulations, suitable for administration onto the skin and nails and into the vagina. The pharmaceutical forms most widely investigated are 1% ciclopirox olamine cream and 8% ciclopirox acid nail lacquer, but lotion, spray, shampoo, pessary, solution, gel and douche formulations have also been used. Ciclopirox penetrates into the deep layers of the skin, mucosal membranes and nail keratin, reaching concentrations exceeding the minimal fungicidal concentrations for most medically important fungi. A large number of clinical trials were and are still being performed with ciclopirox, starting in the early 1980s. Ciclopirox was first developed for fungal skin infections and vaginal candidiasis, and is currently well established in these indications. More recently, the drug has been clinically investigated in seborrhoeic dermatitis and onychomycosis, showing good efficacy and excellent tolerability. Emphasis in this review is given to a ciclopirox medicated nail lacquer, which is based on an original technology and has superior properties in terms of its affinity to keratin and nail permeation. It has been found to have superior efficacy and safety to another commercially available formulation in the treatment of onychomycosis. The safety features of ciclopirox are well known. The topical drug is devoid of systemic adverse reactions. Mild local reactions characterized by a burning sensation of the skin, irritation, redness, pain or pruritus, generally in less than 5% of treated patients, can be observed following skin and vaginal application. With nail application, the most common adverse event is the appearance of mild erythema in 5% of the treated population. As a general conclusion...

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Behandlung von therapieresistenten Verrucae vulgares mit einem Ciclopirox-haltigen Lack

Abstract: Our data suggest that a ciclopirox lacquer may be helpful in the treatment of common warts. However, the data have to be confirmed in a randomized controlled trial in the future.

Cited by 3 publications

References 13 publications

The antifungal drug ciclopirox inhibits deoxyhypusine and proline hydroxylation, endothelial cell growth and angiogenesis in vitro

The antifungal drug ciclopirox inhibits deoxyhypusine and proline hydroxylation, endothelial cell growth and angiogenesis in vitro

The HAG Mechanism: A Molecular Rationale For The Therapeutic Application Of Iron Chelators In Human Diseases Involving the 2-Oxoacid Utilizing Dioxygenases

Ciclopirox

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