BioNanoScience, Journal Year: 2025, Volume and Issue: 15(2)
Published: April 10, 2025
Language: Английский
International Immunopharmacology, Journal Year: 2025, Volume and Issue: 149, P. 114202 - 114202
Published: Feb. 6, 2025
Language: Английский
Citations
5
Chemical Biology & Drug Design, Journal Year: 2025, Volume and Issue: 105(1)
Published: Jan. 1, 2025
ABSTRACT Invasive fungal infections (IFIs) pose significant challenges in clinical settings, particularly due to their high morbidity and mortality rates. The rising incidence of these infections, coupled with increasing antifungal resistance, underscores the urgent need for novel therapeutic strategies. Current drugs target cell membrane, wall, or intracellular components, but resistance mechanisms such as altered drug‐target interactions, enhanced efflux, adaptive cellular responses have diminished efficacy. Recent research has highlighted potential dual inhibitors that simultaneously multiple pathways enzymes involved growth survival. Combining pharmacophores, lanosterol 14α‐demethylase (CYP51), heat shock protein 90 (HSP90), histone deacetylase (HDAC), squalene epoxidase (SE) inhibitors, led development compounds activity reduced resistance. This dual‐target approach, along chemical scaffolds, not only represents a promising strategy combating is also being utilized anticancer agents. review explores new agents employ mono‐, dual‐, multi‐target strategies combat IFIs. We discuss emerging targets, mechanisms, innovative approaches offer hope managing challenging infections.
Language: Английский
Citations
3
ACS Infectious Diseases, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 3, 2025
The emergence of azole resistance and tolerance in pathogenic fungi has emerged as a significant public health concern, emphasizing the urgency for innovative strategies to bolster efficacy azole-based treatments. Drug repurposing stands promising practical avenue advancing antifungal therapy, with potential swift clinical translation. This review offers comprehensive overview synergistic agents uncovered through drug strategies, alongside an in-depth exploration mechanisms by which these augment potency. Drawing from mechanisms, we delineate aimed at enhancing effectiveness, such inhibiting efflux pumps elevate concentrations within fungal cells, intensifying ergosterol synthesis inhibition, mitigating cell azoles, disrupting biological processes extending beyond synthesis. is beneficial development potentiators, it meticulously examines instances provides nuanced discussions on underlying progression potentiators strategies.
Language: Английский
Citations
2
Molecules, Journal Year: 2024, Volume and Issue: 29(5), P. 999 - 999
Published: Feb. 25, 2024
The use of natural compounds to prevent and treat infective diseases is increasing its importance, especially in the case multidrug-resistant (MDR) microorganisms-mediated infections. drug resistance phenomenon today a global problem, so it important have available substances able counteract MDR
Language: Английский
Citations
16
Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14
Published: Feb. 9, 2024
In the last twenty years, there has been a significant increase in invasive fungal infections, which corresponded with expanding population of individuals compromised immune systems. As result, mortality rate linked to these infections remains unacceptably high. The currently available antifungal drugs, such as azoles, polyenes, and echinocandins, face limitations terms their diversity, escalating resistance fungi occurrence adverse effects. Consequently, is an urgent need develop new medications. Vaccines antibodies present promising avenue for addressing due targeted properties ability modulate response. This review investigates structure function cell wall proteins, secreted functional proteins within C. albicans . Furthermore, it seeks analyze current advancements challenges macromolecular drugs identify targets effective management candidiasis.
Language: Английский
Citations
10
Advanced Science, Journal Year: 2023, Volume and Issue: 10(35)
Published: Oct. 24, 2023
Abstract Candida albicans ( C. ), a ubiquitous polymorphic fungus in humans, causes different types of candidiasis, including oral candidiasis (OC) and vulvovaginal (VVC), which are physically mentally concerning financially costly. Thus, developing alternative antifungals that prevent drug resistance induce immunity to eliminate biofilms is crucial. Herein, novel membrane‐targeted aggregation‐induced emission (AIE) photosensitizer (PS), TBTCP‐QY, developed for highly efficient photodynamic therapy (PDT) candidiasis. TBTCP‐QY has high molar absorption coefficient an excellent ability generate 1 O 2 •OH, entering the interior due its permeability. Furthermore, can efficiently inhibit biofilm formation by suppressing expression genes related adhesion ALS3 , EAP1 HWP1 invasion SAP1 SAP2 MDR1 ) also advantageous eliminating potential fungal treat clinical infectious diseases. TBTCP‐QY‐mediated PDT targets OC VVC vivo mouse model, induces immune response, relieves inflammation, accelerates healing mucosal defects combat infections caused clinically isolated fluconazole‐resistant strains. Moreover, demonstrates biocompatibility, suggesting applications treatment VVC.
Language: Английский
Citations
19
Biomolecules, Journal Year: 2023, Volume and Issue: 13(11), P. 1572 - 1572
Published: Oct. 24, 2023
Invasive fungal infections present a significant risk to human health. The current arsenal of antifungal drugs is hindered by drug resistance, limited range, inadequate safety profiles, and low oral bioavailability. Consequently, there an urgent imperative develop novel medications for clinical application. This comprehensive review provides summary the properties mechanisms exhibited natural polyketides, encompassing macrolide polyethers, polyether xanthone linear hybrid polyketide non-ribosomal peptides, pyridine derivatives. Investigating compounds their derivatives has demonstrated remarkable efficacy promising application as agents.
Language: Английский
Citations
18
Antioxidants, Journal Year: 2024, Volume and Issue: 13(2), P. 223 - 223
Published: Feb. 9, 2024
Candida albicans, a prominent opportunistic pathogenic fungus in the human population, possesses capacity to induce life-threatening invasive candidiasis individuals with compromised immune systems despite existence of antifungal medications. When faced macrophages or neutrophils, C. albicans demonstrates its capability endure oxidative stress through utilization antioxidant enzymes. Therefore, enhancement innate cells against presents promising therapeutic approach for treatment candidiasis. In this study, we conducted comprehensive analysis library drugs approved by Food and Drug Administration (FDA). We discovered that halofantrine hydrochloride (HAL) can augment properties damage agents (plumbagin, menadione, H2O2) suppressing response reactive oxygen species (ROS). Furthermore, our investigation revealed inhibitory mechanism HAL on is dependent Cap1. addition, activity has been observed Galleria mellonella infection model. These findings provide evidence targeting augmenting fungicidal hold promise as effective strategies.
Language: Английский
Citations
7
Antibiotics, Journal Year: 2023, Volume and Issue: 12(12), P. 1675 - 1675
Published: Nov. 28, 2023
Candida albicans filamentation plays a significant role in developing both mucosal and invasive candidiasis, making it crucial virulence factor. Consequently, exploring identifying inhibitors that impede fungal hyphal formation presents an intriguing approach toward antifungal strategies. In line with this anti-filamentation strategy, we conducted comprehensive screening of library FDA-approved drugs to identify compounds possess inhibitory properties against growth. The compound octenidine dihydrochloride (OCT) exhibits potent inhibition growth C. across different hyphae-inducing media at concentrations below or equal 3.125 μM. This remarkable effect extends biofilm the disruption mature biofilm. mechanism underlying OCT’s is likely attributed its capacity ergosterol biosynthesis induce generation reactive oxygen species (ROS), compromising integrity cell membrane. Furthermore, has been observed OCT demonstrates protective attributes candidiasis Galleria mellonella larvae through proficient eradication colonization infected G. by impeding formation. Although additional investigation required mitigate toxicity mammals, possesses considerable promise as inhibitor candidiasis.
Language: Английский
Citations
15
Microbes and Infection, Journal Year: 2023, Volume and Issue: 26(1-2), P. 105234 - 105234
Published: Oct. 7, 2023
The World Health Organization (WHO) declared certain fungal pathogens as global health threats for the next decade. Candida auris (C. auris) is a newly emerging skin-tropic multidrug-resistant pathogen that can cause life-threatening infections of high mortality in hospitals and healthcare settings. Here, we address an unmet need present novel native ex vivo skin models, thus extending previous C. auris-host interaction studies. We exploit histology immunofluorescence analysis biopsies human adult fetal, well mouse origin infected with via distinct routes. demonstrate intact barrier efficiently protects from penetration invasion. Although readily grows on skin, it reach deeper layers only upon physical disruption by needling or through otherwise damaged skin. By contrast, not necessary Importantly, show undergoes morphogenetic changes penetration, acquires pseudohyphal growth phenotypes dermal layers. Taken together, this new model toolset yields insights into colonization, adhesion, invasion properties versus results form crucial basis future studies immune defense to colonizing pathogens, offer options testing action efficacy topical antimicrobial compound formulations.
Language: Английский
Citations
14