Selected N-substituted benzisoselenazol-3(2H)-ones possess anti-mycotic activity in vitro and in a mouse model of vulvovaginal candidiasis - presented by Prof Blase Billack

Selected N-substituted benzisoselenazol-3(2H)-ones possess anti-mycotic activity in vitro and in a mouse model of vulvovaginal candidiasis

Prof Blase Billack

Prof Blase Billack
New Advances in Medicinal Chemistry: Bioactive Compounds and Exploitable Targets
Host
Anti-Cancer Agents in Medicinal Chemistry, Bentham Science Publishers (United Arab Emirates)
DateFriday, June 20, 2025 1:00 PM to 1:30 PM (UTC)
Live eventThe live event and other events in this series can be joined through this page.
Anti-Cancer Agents in Medicinal Chemistry
Selected N-substituted benzisoselenazol-3(2H)-ones possess anti-mycotic activity in vitro and in a mouse model of vulvovaginal candidiasis
Prof Blase Billack
Blase Billack
Saint John's Catholic University, College of Pharmacy and Health Sciences

Associated Nanomedicine Nanotechnology Biology and Medicine article

S. Menon et al. (2021) Evaluation of the antifungal activity of an ebselen-loaded nanoemulsion in a mouse model of vulvovaginal candidiasis. Nanomedicine Nanotechnology Biology and Medicine
Article of record

The global rise of virulent and drug-resistant Candida albicans strains has intensified the need for novel antifungal agents, especially as fluconazole (FLU) resistance increases in susceptible populations. Ebselen (EB), an organoselenium compound, has emerged as a promising candidate due to its inhibition of the fungal plasma membrane H⁺-ATPase (Pma1p), a target not addressed by current antifungals. However, EB’s poor solubility and off-target effects in mammalian systems limit its therapeutic potential. To overcome these challenges, our studies pursued two parallel strategies: the development of EB nanoformulations and the synthesis of novel EB analogs.

EB-loaded self-nanoemulsifying preconcentrate (EB-SNEP) demonstrated potent antifungal activity in a murine vulvovaginal candidiasis (VVC) model, significantly reducing fungal burden (~800-fold) without signs of toxicity in host tissues or probiotic flora. Concurrently, libraries of EB analogs, including G- and CHB-series compounds, were screened in vitro for activity against both FLU-sensitive and -resistant C. albicans strains. Compounds such as G20 and CHB6 showed superior efficacy (MIC as low as 3.1 µM) and targeted Pma1p-dependent acidification mechanisms. Although some analogs displayed slightly reduced growth inhibition relative to EB, they may offer better host tolerability by minimizing non-specific interactions.

Taken together, our findings support organoselenium-based inhibitors as a compelling class of antifungal agents. Both EB nanoformulations and selected analogs warrant further development as treatments for FLU-resistant candidiasis, with the dual benefits of novel target specificity and improved delivery profiles.

References
  • 1.
    S. Menon et al. (2021) Evaluation of the antifungal activity of an ebselen-loaded nanoemulsion in a mouse model of vulvovaginal candidiasis. Nanomedicine Nanotechnology Biology and Medicine
  • 2.
    X. Liang et al. (2023) Nanoformulation of A Novel Potent Ebselen Analog for Treatment of Vulvovaginal Candidiasis. Nanomedicine
  • 3.
    S. Thenin-Houssier et al. (2016) Ebselen, a Small-Molecule Capsid Inhibitor of HIV-1 Replication. Antimicrobial Agents and Chemotherapy
  • 4.
    G. Chan et al. (2007) Evaluation of the antimicrobial activity of ebselen: Role of the yeast plasma membrane H+‐ATPase. Journal of Biochemical and Molecular Toxicology
  • 5.
    B. Billack et al. (2009) Growth Inhibitory Action of Ebselen on Fluconazole-ResistantCandida albicans: Role of the Plasma Membrane H+-ATPase. Microbial Drug Resistance
  • 6.
    S. Menon et al. (2021) Antifungal Activity of Novel Formulations Based on Terpenoid Prodrugs against C. albicans in a Mouse Model. Pharmaceutics
  • 7.
    X. Liang et al. (2023) Selected N-Terpenyl Organoselenium Compounds Possess Antimycotic Activity In Vitro and in a Mouse Model of Vulvovaginal Candidiasis. Molecules
  • 8.
    X. Liang et al. (2024) N-3-Methylbutyl-benzisoselenazol-3(2H)-one Exerts Antifungal Activity In Vitro and in a Mouse Model of Vulvovaginal Candidiasis. Current Issues in Molecular Biology
  • 9.
    N. N. Orie et al. (2017) In vitro assessment of the growth and plasma membrane H+‐ATPase inhibitory activity of ebselen and structurally related selenium‐ and sulfur‐containing compounds in Candida albicans. Journal of Biochemical and Molecular Toxicology
  • 10.
    B. Billack et al. (2010) Evaluation of the antifungal and plasma membrane H+-ATPase inhibitory action of ebselen and two ebselen analogs in S. cerevisiae cultures. Journal of Enzyme Inhibition and Medicinal Chemistry
Date & time
Jun
20
2025
Friday, June 20, 2025 1:00 PM to 1:30 PM (UTC)
Details
Listed event This event is open to all
Recorded Available to all
Q&A Open on this page for 1 day after the event