Sulconazole 1% cream

Drug repurposing in oncology is a strategy that attempts to identify new therapeutic uses of drugs already approved for other diseases to treat cancer. This strategy has gained interest because of its potential to reduce costs and accelerate the development of oncology treatments. This research topic aims to provide information on repositioned drugs in different types of cancer, to personalize and improve cancer therapies. Ten manuscripts in this issue examine various but interconnected aspects of drug repurposing, highlighting the rapid advancement of the field and increasing complexity.Common tumors refer to cancers with high incidence and prevalence across global populations, making them some of the most frequently diagnosed malignancies.These typically include solid tumors such as breast, lung, colorectal, prostate, ovarian, pancreatic, liver, and bladder cancers. Characterized by well-established clinical and biological profiles, these tumors are often supported by robust preclinical models and extensive clinical trial data. Due to their prevalence and clinical impact, they are strong candidates for drug repurposing to enhance outcomes, particularly in resistant cases or when treatment options are limited.In this sense, triple negative breast cancer (TNBC) is usually an aggressive and difficult-to-treat cancer. On this topic, Carrion-Estrada et al. demonstrated a compelling strategy for targeting TNBC by stabilizing the oncogenic K-Ras4B G13D/PDE6δ complex using novel compounds (C14 and P8). These agents suppressed tumor growth in both in vitro and in vivo models, including resistant TNBC subtypes, highlighting their potential as adjuvant treatments when standard therapies fail (https://doi.org/10.3389/fonc.2024.1341766). In a related effort to expand treatment options through drug repositioning, Hajihosseini and coworkers conducted a meta-analysis showing that olaparib, typically used in BRCA1/2-mutant breast and ovarian cancer, improved progression-free survival (PFS) when used as monotherapy in lung cancer compared to combination regimens with durvalumab or gefitinib (https://doi.org/10.3389/fonc.2025.1505889). In parallel, Pernot et al.explored an immunomodulatory approach through the repurposing of sulconazole, an antifungal compound that inhibits PD-1 expression in immune and cancer cells by blocking NF-κB and calcium signaling. The ability of sulconazole to restore immune activity while repressing malignant traits further highlights the value of nontraditional compounds in oncology, especially for immunologically evasive tumors (https://doi.org/10.3389/fimmu.2023.1278630).Complementing these findings, Villegas Vásquez et al. provided a comprehensive review on drug repositioning for ovarian cancer, emphasizing the critical role of cell line and animal models in preclinical drug screening. Although clinical application remains in early stages, these models are key to developing future therapies aimed at improving outcomes in patients with gynecologic cancers (https://doi.org/10.3389/fonc.2024.1514120).At the genomic level, Martinez-Montiel and colleagues discussed a paradigm shift by focusing on alternative splicing events in prostate cancer. As splicing errors increasingly emerge as hallmarks of malignancy, this review advocates for the development of diagnostics and therapies that target cancer-specific splicing isoforms, an especially timely strategy given the rising global burden of disease in low-resource settings (https://doi.org/10.3389/fonc.2025.1520985). Additionally, Sánchez-Marín et al. discussed thyroid cancer (TC) at the genomic levels and identified 13 genes with missense mutations and 10 for gene fusions as potential therapeutic targets for drug repositioning. This which represents promising area for

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Esophageal cancer is the seventh most common cancer in the world. Although traditional treatment methods such as radiotherapy and chemotherapy have good effects, their side effects and drug resistance remain problematic. The repositioning of drug function provides new ideas for the research and development of anticancer drugs. We previously showed that the Food and Drug Administration-approved drug sulconazole can effectively inhibit the growth of esophageal cancer cells, but its molecular mechanism is not clear. Here, our study demonstrated that sulconazole had a broad spectrum of anticancer effects. It can not only inhibit the proliferation but also inhibit the migration of esophageal cancer cells. Both transcriptomic sequencing and proteomic sequencing showed that sulconazole could promote various types of programmed cell death and inhibit glycolysis and its related pathways. Experimentally, we found that sulconazole induced apoptosis, pyroptosis, necroptosis, and ferroptosis. Mechanistically, sulconazole triggered mitochondrial oxidative stress and inhibited glycolysis. Finally, we showed that low-dose sulconazole can increase radiosensitivity of esophageal cancer cells. Taken together, these new findings provide strong laboratory evidence for the clinical application of sulconazole in esophageal cancer.

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Solid lipid nanoparticles (SLNs) have the advantages of a cell-specific delivery and sustained release of hydrophobic drugs that can be exploited against infectious diseases. The topical delivery of hydrophobic drugs needs pharmaceutical strategies to enhance drug permeation, which is a challenge faced by conventional formulations containing a drug suspended in gel, creams or ointments. We report the fabrication and optimization of SLNs with sulconazole (SCZ) as a model hydrophobic drug and then a formulation of an SLN-based topical gel against fungal infections. The SLNs were optimized through excipients of glyceryl monostearate and Phospholipon® 90 H as lipids and tween 20 as a surfactant for its size, drug entrapment and sustained release and resistance against aggregation. The SCZ-SLNs were physically characterized for their particle size (89.81 ± 2.64), polydispersity index (0.311 ± 0.07), zeta potential (−26.98 ± 1.19) and encapsulation efficiency (86.52 ± 0.53). The SCZ-SLNs showed sustained release of 85.29% drug at the 12 h timepoint. The TEM results demonstrated spherical morphology, while DSC, XRD and FTIR showed the compatibility of the drug inside SLNs. SCZ-SLNs were incorporated into a gel using carbopol and were further optimized for their rheological behavior, pH, homogeneity and spreadability on the skin. The antifungal activity against Candida albicans and Trichophyton rubrum was increased in comparison to a SCZ carbopol-based gel. In vivo antifungal activity in rabbits presented faster healing of skin fungal infections. The histopathological examination of the treated skin from rabbits presented restoration of the dermal architecture. In summary, the approach of formulating SLNs into a topical gel presented an advantageous drug delivery system against mycosis.

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Imidazole derivatives are commonly used as antifungal agents. Here, we aimed to investigate the functions of imidazole derivatives on macrophage lineage cells. We assessed the expression levels of inflammatory cytokines in mouse monocyte/macrophage lineage (RAW264.7) cells. All six imidazole derivatives examined, namely ketoconazole, sulconazole, isoconazole, luliconazole, clotrimazole, and bifonazole, reduced the expression levels of inflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor-α, after induction by lipopolysaccharide (LPS) in RAW264.7 cells. These imidazole derivatives also induced cell death in RAW264.7 cells, regardless of the presence or absence of LPS. Since the cell death was characteristic in morphology, we investigated the mode of the cell death. An imidazole derivative, sulconazole, induced gasdermin D degradation together with caspase-11 activation, namely, pyroptosis in RAW264.7 cells and peritoneal macrophages. Furthermore, priming with interferon-γ promoted sulconazole-induced pyroptosis in RAW264.7 cells and macrophages and reduced the secretion of the inflammatory cytokine, IL-1β, from sulconazole-treated macrophages. Our results suggest that imidazole derivatives suppress inflammation by inducing macrophage pyroptosis, highlighting their modulatory potential for inflammatory diseases.

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The overexpression of the immunoinhibitory receptor programmed death-1 (PD1) on T-cells is involved in immune evasion in cancer. The use of anti-PD-1/PDL-1 strategy has deeply changed the therapies of cancers and patient survival. However, their efficacy diverges greatly along with tumor type and patient populations. Thereby, novel treatments are needed to interfere with the anti-tumoral immune responses and propose an adjunct therapy. In the current study, we found that the antifungal drug Sulconazole (SCZ) inhibits PD-1 expression on activated PBMCs and T cells at the RNA and protein levels. SCZ repressed NF-κB and calcium signaling, both, involved in the induction of PD-1. Further analysis revealed cancer cells treatment with SCZ inhibited their proliferation, and migration and ability to mediate tumor growth in zebrafish embryos. SCZ found also to inhibit calcium mobilization in cancer cells. These results suggest the SCZ therapeutic potential used alone or as adjunct strategy to prevent T-cell exhaustion and promotes cancer cell malignant phenotype repression in order to improve tumor eradication.

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ABSTRACT Pathogenic fungi pose significant societal challenges due to limited therapeutic targets resulting from the eukaryotic nature of fungi. This limitation emphasizes the importance of enhancing susceptibility to inhibitors of Cyp51, a crucial enzyme in ergosterol biosynthesis targeted by azole antifungals. In Cyp51 isozyme deletion strains (Δ cyp51A and Δ cyp51B ) of Trichophyton rubrum , the predominant dermatophyte species, we found that Cyp51B is essential for basal mycelial growth, while Cyp51A functions as an inducible isozyme associated with azole tolerance. Based on these differential functions, we hypothesized that each isozyme would show distinct susceptibility to azole antifungals. Our study demonstrated that most azoles exhibited increased antifungal activity against Δ cyp51A , while select agents demonstrated increased antifungal activity against Δ cyp51B . Remarkably, fluconazole, sulconazole, and imazalil exhibited relatively increased activity against Δ cyp51A , whereas prochloraz demonstrated increased activity against Δ cyp51B . Combining these isozyme-selective agents exerted synergistic effects against the wild-type strain and the parent ku80 -knockout strain but not against individual Cyp51 knockout mutants. Our data revealed that the two Cyp51 isozymes can be selectively inhibited by different azole antifungals, resulting in a synergistic effect when combined. This synergistic effect was also observed on another fungal species, Aspergillus welwitschiae , which also has two Cyp51 isozymes. These data demonstrate that combining azole antifungals with different Cyp51 isozyme selectivities exerts synergistic effects against fungi possessing multiple Cyp51 isozymes. These findings advance antifungal therapeutic strategies by demonstrating that the combination of antifungals with different Cyp51 isozyme selectivities offers a promising approach for treating fungal infections, opening new avenues for isozyme-specific drug development.

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