Triazole-hydroxy naphthalimide hybrid as a fluorescent molecular tool for antifungal therapy and imaging: Experimental and theoretical investigations
Document Type
Article
Publication Title
Journal of Molecular Structure
Abstract
The rising incidence of fungal infections and growing resistance to current treatments highlight the need for accurate identification of fungal pathogens to ensure the selection of appropriate antifungal therapy. Therefore, specific fluorescent dyes for targeted fungal identification along with new antifungal agents are crucial for preventing fungal resistance, effective treatment, and reducing mortality rates. To address these challenges, 2-(3-amino-1H-1,2,4-triazol-5-yl)-5-hydroxy-1H-benzo[de]isoquinoline-1,3(2H)-dione (THN) is designed as a new structural hybrid to combine the antifungal properties of guanazole and the fluorescent features of 1,8-naphthalimide. THN prepared through an easy one-step imidation reaction between guanazole and 3-hydroxy-1,8-naphthalic anhydride was used in the wet mount preparation of Candida albicans, emphasizing the importance of developing biocompatible fluorophores for advanced imaging techniques to mitigate autofluorescence, enhance image quality, and eliminate the need for incubation steps. Further, the ability of THN as an antifungal agent was assessed through comprehensive computational approaches using chitin synthase (CHS), a vital enzyme in maintaining fungal cell wall integrity, and a promising target for antifungal therapies. The molecular docking results illustrate superior binding affinity (-9.4 kcal/mol) of THN, forming stable molecular interactions within the CHS active site compared to the standard antifungal agents: fluconazole (-6.7 kcal/mol) and nikkomycin Z (-8.7 kcal/mol). In addition, molecular dynamics simulations establish stable interactions between THN and CHS, demonstrating a binding free energy of -142.67 kcal/mol. Furthermore, THN displays therapeutic efficacy to inhibit the growth of C. albicans at a minimum concentration of 0.307 mM.
DOI
10.1016/j.molstruc.2025.143505
Publication Date
12-25-2025
Recommended Citation
G, Smitha; M, Ranjana; Shenoy, Thripthi Nagesh; and Sunil, Dhanya, "Triazole-hydroxy naphthalimide hybrid as a fluorescent molecular tool for antifungal therapy and imaging: Experimental and theoretical investigations" (2025). Open Access archive. 11564.
https://impressions.manipal.edu/open-access-archive/11564
