BioNanoScience, Journal Year: 2025, Volume and Issue: 15(2)
Published: April 10, 2025
Language: Английский
Marine Drugs, Journal Year: 2024, Volume and Issue: 22(4), P. 180 - 180
Published: April 17, 2024
The incidence of invasive fungal diseases (IFDs) is on the rise globally, particularly among immunocompromised patients, leading to significant morbidity and mortality. Current clinical antifungal agents, such as polyenes, azoles, echinocandins, face increasing resistance from pathogenic fungi. Therefore, there a pressing need for development novel drugs. Marine-derived secondary metabolites represent valuable resources that are characterized by varied chemical structures pharmacological activities. While numerous compounds exhibiting promising activity have been identified, comprehensive review elucidating their specific underlying mechanisms remains lacking. In this review, we compiled summary derived marine organisms, highlighting diverse action targeting various cellular components, including cell wall, membrane, mitochondria, chromosomes, drug efflux pumps, several biological processes, vesicular trafficking growth hyphae biofilms. This helpful subsequent drugs due its organisms.
Language: Английский
Citations
6
Life Sciences, Journal Year: 2024, Volume and Issue: 348, P. 122699 - 122699
Published: May 6, 2024
Azoles have been widely employed for the treatment of invasive fungal diseases; however, their efficacy is diminished as pathogenic fungi tolerate them due to fungistatic properties. Geldanamycin (GdA) can render azoles fungicidal by inhibiting ATPase and molecular chaperone activities heat shock protein 90 (Hsp90). Nonetheless, clinical applicability GdA restricted its cytotoxic ansamycin scaffold structure, induction cytoprotective responses, conservative nature Hsp90. Hence, it imperative elucidate mechanism action confer properties mitigate toxic adverse effects associated with GdA. Through various experimental methods, including construction gene-deleted Candida albicans mutants, in vitro drug sensitivity experiments, Western blot analysis, reactive oxygen species (ROS) assays, succinate dehydrogenase activity we identified Hsp90 client proteins tolerance C. azoles. It was observed that effectively hindered entry into mitochondria, resulting alleviation inhibitory effect on dehydrogenase. Consequently, activation led an increased production ROS. within thereby facilitating antifungal against albicans. This research presents a novel approach conferring azoles, which involves specifically disrupting interaction between rather than employing non-specific inhibition
Language: Английский
Citations
6
Research, Journal Year: 2024, Volume and Issue: 7
Published: Jan. 1, 2024
Candida albicans is an opportunistic fungal pathogen of humans. It causes a variety infections ranging from superficial mucocutaneous conditions to severe systemic diseases that result in substantial morbidity and mortality. This frequently forms biofilms resistant antifungal drugs the host immune system, leading treatment failures. Recent research has demonstrated potential nanorobots penetrate biological barriers disrupt biofilms. In this perspective paper, we provide brief overview recent breakthroughs for candidiasis discuss current challenges prospects.
Language: Английский
Citations
5
Small, Journal Year: 2024, Volume and Issue: 20(32)
Published: March 19, 2024
Abstract Chronic wounds of significant severity and acute injuries are highly vulnerable to fungal infections, drastically impeding the expected wound healing trajectory. The clinical use antifungal therapeutic drug is hampered by poor solubility, high toxicity adverse reactions, thereby necessitating urgent development novel therapy strategy. Herein, this study proposes a new strategy enhance bioactivity small‐molecule drugs based on multifunctional metal nanozyme engineering, using amphotericin B (AmB) as an example. AmB‐decorated gold nanoparticles (AmB@AuNPs) synthesized facile one‐pot reaction strategy, AmB@AuNPs exhibit superior peroxidase (POD)‐like enzyme activity, with maximal rates (V max ) 3.4 times higher than that AuNPs for catalytic H 2 O . Importantly, enzyme‐like activity significantly enhanced properties AmB, minimum inhibitory concentrations against Candida albicans ( C. Saccharomyces cerevisiae S. W303 reduced 1.6‐fold 50‐fold, respectively, compared AmB alone. Concurrent in vivo studies conducted fungal‐infected mice underscored fundamentally ability biosafety AmB@AuNPs. proposed engineering nanozymes has great potential infections related diseases.
Language: Английский
Citations
4
Antioxidants, Journal Year: 2024, Volume and Issue: 13(6), P. 667 - 667
Published: May 29, 2024
Fluconazole (FLC) is extensively employed for the prophylaxis and treatment of invasive fungal infections (IFIs). However, fungistatic nature FLC renders pathogenic fungi capable developing tolerance towards it. Consequently, converting into a fungicidal agent using adjuvants assumes significance to circumvent resistance perpetuation infections. This drug repurposing study has successfully identified pitavastatin calcium (PIT) as promising adjuvant enhancing activity from comprehensive library 2372 FDA-approved drugs. PIT could render even at concentrations low 1 μM. The median lethal dose (LD50) was determined be 103.6 mg/kg. We have discovered that achieves its synergistic effect by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, thereby impeding ubiquinone biosynthesis, inducing reactive oxygen species (ROS) generation, triggering apoptosis, disrupting Golgi function. Candida albicans strain demonstrated notable infect mice found effectively augmented antifungal efficacy against IFIs. an illustrative example how drugs can eliminate FLC.
Language: Английский
Citations
4
Journal of Drug Delivery Science and Technology, Journal Year: 2024, Volume and Issue: 102, P. 106365 - 106365
Published: Nov. 1, 2024
Language: Английский
Citations
4
Fundamental Research, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 1, 2025
Language: Английский
Citations
0
Medicina Clínica (English Edition), Journal Year: 2025, Volume and Issue: 164(2), P. 76 - 83
Published: Jan. 1, 2025
Language: Английский
Citations
0
Journal of Photochemistry and Photobiology B Biology, Journal Year: 2025, Volume and Issue: unknown, P. 113105 - 113105
Published: Jan. 1, 2025
Language: Английский
Citations
0
European Journal of Pharmaceutical Sciences, Journal Year: 2025, Volume and Issue: 207, P. 107041 - 107041
Published: Feb. 12, 2025
Heat shock protein 90 (Hsp90) is a pivotal virulence factor in pathogenic fungi, playing significant role conferring drug resistance. However, due to the high amino acid sequence similarity between fungal and mammalian Hsp90, targeting intracellular Hsp90 therapeutically associated with marked toxic side effects, thereby limiting clinical application. Studies have demonstrated that can be secreted as extracellular (eHsp90), which plays crucial infections. Strategies eHsp90 exhibited promising therapeutic outcomes. Unlike targeting, such antifungal approaches operate without cell penetration, circumventing effects Hsp90's conservation. This review summarizes potential secretion pathways of eHsp90, its roles pathogenesis, well development vaccines antibodies eHsp90. The underlines significance infections suggests represents target for infection treatment.
Language: Английский
Citations
0