Review

Authors: Parisa Aris, Yulong Wei, Masoud Mohamadzadeh...

Griseofulvin is an antifungal polyketide metabolite produced mainly by ascomycetes. Since it was commercially introduced in 1959, griseofulvin has been used in treating dermatophyte infections. This fungistatic has gained increasing interest for multifunctional applications in the last decades due to its potential to disrupt mitosis and cell division in human cancer cells and arrest hepatitis C virus replication. In addition to these inhibitory effects, we and others found griseofulvin may enhance ACE2 function, contribute to vascular vasodilation, and improve capillary blood flow. Furthermore, molecular docking analysis revealed that griseofulvin and its derivatives have good binding potential with SARS-CoV-2 main protease, RNA-dependent RNA polymerase (RdRp), and spike protein receptor-binding domain (RBD), suggesting its inhibitory effects on SARS-CoV-2 entry and viral replication. These findings imply the repurposing potentials of the FDA-approved drug griseofulvin in designing and developing novel therapeutic interventions. In this review, we have summarized the available information from its discovery to recent progress in this growing field. Additionally, explored is the possible mechanism leading to rare hepatitis induced by griseofulvin. We found that griseofulvin and its metabolites, including 6-desmethylgriseofulvin (6-DMG) and 4- desmethylgriseofulvin (4-DMG), have favorable interactions with cytokeratin intermediate filament proteins (K8 and K18), ranging from -3.34 to -5.61 kcal mol. Therefore, they could be responsible for liver injury and Mallory body (MB) formation in hepatocytes of human, mouse, and rat treated with griseofulvin. Moreover, the stronger binding of griseofulvin to K18 in rodents than in human may explain the observed difference in the severity of hepatitis between rodents and human.

Topics: Mice; Humans; Rats; Animals; Griseofulvin; Antifungal Agents; SARS-CoV-2; Angiotensin-Converting Enzyme 2; Molecular Docking Simulation; Spike Glycoprotein, Coronavirus; COVID-19; Keratins; RNA-Dependent RNA Polymerase; Polyketides

PubMed: 36296627
DOI: 10.3390/molecules27207034

Review

Authors: D Taplin

Twenty-five years ago many of the topical remedies for superficial mycoses were irritating, toxic, or allergenic. Total x-ray depilation of the scalp was the accepted mode of therapy for tinea capitis. The introduction of topical nystatin for candidiasis and tolnaftate for dermatophytosis were major advances, but tinea capitis, onychomycosis, and chronic tinea pedis still presented problems. Soon after its introduction in 1958, griseofulvin became the definitive form of therapy for all types of dermatophytosis and played a major role in abolishing large-scale epidemics of tinea capitis in some countries. Recently, haloprogin and the imidazole derivatives, miconazole and clotrimazole, which are topically active against dermatophytes and Candida albicans, have become available. Selective indicator media for isolating dermatophytes are useful diagnostic tools, but quicker methods of diagnosis which require little interpretation are still lacking. Epidemiologic studies in Vietnam again revealed the effects of climate and occlusion on the prevalence, incidence, and severity of superficial mycoses and led to renewed interest in host susceptibility, environment, and prevention of infections.

Topics: Administration, Topical; Adult; Animals; Antifungal Agents; Arthrodermataceae; Candidiasis; Dermatomycoses; Female; Griseofulvin; Hair Removal; Humans; Male; Nystatin

PubMed: 778288
DOI: 10.1111/1523-1747.ep12513020

Review

Authors: Nanqiong Yu, Yixiao Fu, Qingkui Fan...

Griseofulvin (GF), which is mainly extracted from , is a heat-resistant, chlorine-containing non-polyene antifungal antibiotic. Previous research shows that GF has a variety of pharmacological effects, such as anti-inflammatory, antifungal, antiviral, and antitumor effects. In recent years, GF has received extensive attention for its antitumor effects as a natural compound, offering a low price, a wide range of uses, and other beneficial characteristics. However, no comprehensive review of GF pharmacological activity in tumors has been published so far. In order to fully elucidate the antitumor activities of GF, this review focuses on the antitumor potential and toxicity of GF and its derivatives, based on a literature search using PubMed, Web of Science, and other databases, to lay a good foundation for further research of GF and the development of new drugs for antitumor activities.

PubMed: 39314753
DOI: 10.3389/fphar.2024.1459539

Review

Authors: Takashi Harada

Although onychomycoses are caused by dermatophytes, yeasts or non-dermatophyte molds, tinea unguium describes chronic fungal infections by dermatophytes only. Tinea unguium is a common fungal infection of the nail plate or nail bed with increasing prevalence worldwide. It is not self-limited and shows a higher frequency among the elderly population. In Japan, approximately 10% of the entire population is estimated to have tinea unguium. During the period when only griseofulvin was available for treatment, it was a very difficult disease to treat. Since in the 1990's, however, the introduction of new oral antifungals, itraconazole and terbinafine, initiated a new era in the treatment of tinea unguium. Many excellent textbooks, review articles, and original articles have already been published. This paper considers the circumstances in Japan, epidemiology, causative agents including non-dermatophyte molds, differential diagnosis, diagnostic techniques, the quality of life of the patients with tinea unguium, and then the treatment options are reviewed again.

Topics: Aged; Antifungal Agents; Humans; Itraconazole; Naphthalenes; Onychomycosis; Terbinafine

PubMed: 21788720
DOI: 10.3314/jjmm.52.77

Authors: Sardar Pasha Sheik Pran Babu, Darcy White, Timothy W Corson...

Ferrochelatase (FECH) is the terminal enzyme in heme biosynthesis. We previously showed that FECH is required for endothelial cell growth in vitro and choroidal neovascularization in vivo. But FECH has not been explored in retinal neovascularization, which underlies diseases like proliferative diabetic retinopathy and retinopathy of prematurity. Here, we investigated the inhibition of FECH using genetic and chemical approaches in the oxygen-induced retinopathy (OIR) mouse model. In OIR mice, FECH expression is upregulated and co-localized with neovascular tufts. Partial loss-of-function Fech  mutant mice showed reduced retinal neovascularization and endothelial cell proliferation in OIR. An intravitreal injection of the FECH inhibitor N-methyl protoporphyrin had similar effects. Griseofulvin is an antifungal drug that inhibits FECH as an off-target effect. Strikingly, intravitreal griseofulvin decreased both pathological tuft formation and areas of vasoobliteration compared to vehicle, suggesting potential as a FECH-targeting therapy. Ocular toxicity studies revealed that intravitreal injection of griseofulvin in adult mice does not disrupt retinal vasculature, function, or morphology. In sum, mutation and chemical inhibition of Fech reduces retinal neovascularization and promotes physiological angiogenesis, suggesting a dual effect on vascular repair upon FECH inhibition, without ocular toxicity. These findings suggest that FECH inhibitors could be repurposed to treat retinal neovascularization.

Topics: Animals; Cell Hypoxia; Cell Proliferation; Female; Ferrochelatase; Griseofulvin; Mice; Mice, Inbred C57BL; Retina; Retinal Neovascularization

PubMed: 32716567
DOI: 10.1096/fj.202000964R

Authors: Dipti Das, Anupam Das, Nilay Kanti Das...

Topics: Anti-Inflammatory Agents; Antifungal Agents; Child, Preschool; Griseofulvin; Humans; Male; Prednisolone; Scalp; Tinea Capitis

PubMed: 24953594
DOI: No ID Found

Authors: F A Ive, R Marks

Fourteen cases are described in which the local application of corticosteroid preparations to ringworm infections of the skin have resulted in unusual clinical pictures. A kerion-like lesion due to Trichophyton rubrum, intertriginous infections simulating candidiasis and due to Epidermophyton floccosum, and pictures resembling poikiloderma, papular rosacea, and indeterminate leprosy are among the changes that were seen in these patients.

Topics: Adolescent; Adult; Aged; Betamethasone; Diagnosis, Differential; Eczema; Epidermophyton; Female; Fluocinolone Acetonide; Glucocorticoids; Griseofulvin; Humans; Keratins; Male; Middle Aged; Skin Diseases; Tinea; Triamcinolone Acetonide; Trichophyton; Valerates

PubMed: 5662546
DOI: 10.1136/bmj.3.5611.149