Clinical fungal infections have become more frequent in recent years especially among patients with compromised immune systems like those suffering from HIV, cancer, or who have undergone organ transplants. Life-threatening fungal infections impact 13 million individuals each year which results in 1.6 million deaths according to statistical data. The mortality rate for fungal infections stays at 67% despite having standardized antifungal treatments.
Existing antifungal treatments like azole, echinocandin, polyene, and flucytosine cannot adequately treat systemic infections because drug targets remain limited in number. The majority of therapeutic approaches focus on treating just Candida and Aspergillus fungal species. The effectiveness of these drugs is reduced by toxicity issues along with drug interactions and antifungal resistance which together limit their clinical effectiveness and complicate treatment strategies. The past two decades have seen limited antifungal drug target discoveries which restricted novel antifungal drug development while innovative drugs entered markets slowly.
Innovative drug approaches including nanoparticles and natural products along with drug repurposing show potential because they improve treatment efficacy while reducing resistance.
Novel Antifungal Compounds
Compound K21: K21 is a quaternary ammonium silica compound containing tetraethoxysilane and has been used as a broad-spectrum antiviral and antimicrobial agent. It primarily acts through membrane disruption, leading to rapid fungal cell death. It exhibits significant antifungal activity against fluconazole-sensitive and resistant Candida species, including Candida albicans, Candida glabrata, and Saccharomyces cerevisiae. When combined with fluconazole, it produces a synergistic effect.
Olorofim (F9013_118): A member of the orotomide class of antifungal agents, originally identified through in vitro screening of small molecules against Aspergillus species. It selectively inhibits dihydroorotate dehydrogenase, disrupting pyrimidine biosynthesis, cell wall remodeling, and inducing apoptosis. Olorofim is a strong candidate for treating drug-resistant fungal pathogens and is currently in Phase II clinical trials.
VT-1161 (Otetaconazole): A novel tetrazole antifungal drug designed to target a key component of the fungal cell membrane. VT-1161 inhibits traditional azole antifungal drugs such as fluconazole. In recent studies, VT-1161 was found to inhibit biofilm formation by Beauveria bassiana, Klebsiella pneumoniae, and Staphylococcus aureus, as well as dual-species biofilms formed by these pathogens.
T-2307: A novel arylamidine compound with potent antifungal activity against Candida, Cryptococcus, and Aspergillus species. It has shown significant efficacy against Candida tropicalis, a pathogen known for biofilm formation, which enhances its virulence and resistance.
Ibrexafungerp (formerly SCY-078 and MK-3118): A triterpenoid antifungal drug marketed under the name Brexafemme. It is the first oral β-(1,3)-D-glucan synthase inhibitor. The U.S. FDA has approved it for the treatment of vulvovaginal candidiasis and recurrent vulvovaginal candidiasis.
Fosmanogepix (FMGX): FMGX is a prodrug that metabolizes into its active form and targets fungal Gwt1 enzyme, which is crucial for glycosylphosphatidylinositol (GPI) biosynthesis and fungal cell wall integrity. It is effective against multiple pathogens, including fluconazole- and echinocandin-resistant Candida strains and azole-resistant Aspergillus fumigatus. Its high bioavailability allows for both oral and intravenous administration, providing treatment flexibility.
Rezafungin: Formerly known as CD101, this next-generation echinocandin antifungal drug has enhanced pharmacokinetics, allowing for once-weekly dosing. It can be administered via intravenous injection, subcutaneous injection, or topical application. It exhibits broad-spectrum antifungal activity against multiple pathogens, including Candida, Aspergillus, and azole-resistant strains. It is particularly effective against Candida albicans, Candida parapsilosis, Candida glabrata, and Candida tropicalis, showing comparable or superior activity to azoles.
PQA-Az-13: A newly synthesized hybrid antifungal compound designed to combat drug-resistant Candida yeast pathogens. It has not yet been evaluated against other fungal species but has demonstrated strong antifungal activity by disrupting biofilm formation. The minimum inhibitory concentration (MIC) ranges from 0.67 to 1.25 μg/mL, which is lower than that of fluconazole.
AM-2-19 (SF001): A newly developed experimental polyene antifungal drug optimized to retain strong antifungal potency while reducing nephrotoxicity. It allows for higher dosing without significant renal toxicity. AM-2-19 exhibits broad-spectrum antifungal activity, and in animal models of candidiasis, aspergillosis, and mucormycosis, it has shown dose-dependent efficacy—higher doses result in more complete fungal eradication. It represents a significant advancement in antifungal therapy, especially for treating invasive fungal infections in immunocompromised patients.
N′-Phenylhydrazones: A newly synthesized class of antifungal compounds targeting fluconazole-resistant Candida albicans strains. Among the synthesized N′-phenylhydrazone derivatives, several compounds have demonstrated strong antifungal activity, outperforming fluconazole against fluconazole-resistant Beauveria bassiana strains. Compound A11 exhibited the best inhibitory activity.
Innovative Approaches in Antifungal Drug Development
Natural Extracts: Natural antifungal agents are compounds extracted from plants, bacteria, fungi, and other natural sources, evolved to protect host organisms from microbial pathogens, including fungi. These compounds have multiple advantages, including lower toxicity, reduced environmental impact, and potential activity against multiple fungal species. Examples include alkaloids such as γ-pyrone D, thiopeptamide G, polyketides like Dicitrinone E and Plakortide F, peptides such as Rhodopeptins, essential oils like lemongrass oil and citronella oil, and bacterial extracts such as those from Streptomyces species.
Nanomedicine: Nanoparticles and green synthesis materials offer a promising platform for antifungal drug development, particularly antimicrobial nanoparticles with antifungal properties. Examples include magnetic nanoparticles and silver nanoparticles, which exhibit strong antifungal activity.
Antifungal agents at BOC Sciences
| Catalog | Name | Cas |
| B1335-476319 | Nystatin | 1400-61-9 |
| B1370-010028 | Lactoferrin | 146897-68-9 |
| B2695-053623 | Tacrolimus EP Impurity A | 104987-12-4 |
| B0084-057821 | Pneumocandin B0 | 135575-42-7 |
| B0084-060529 | Anidulafungin | 166663-25-8 |
| B0084-060834 | Posaconazole | 171228-49-2 |
| B1335-476174 | Caspofungin acetate | 179463-17-3 |
| B2693-063789 | Isavuconazole | 241479-67-4 |
| B2699-064110 | Decamethoxine | 38146-42-8 |
| B0084-068466 | Ciclopirox ethanolamine | 41621-49-2 |
| B1370-077326 | Amorolfine hydrochloride | 78613-38-4 |
| B0046-464072 | Sertaconazole nitrate | 99592-39-9 |
| B0001-081629 | Dimethomorph | 110488-70-5 |
| B0084-096421 | Ketoconazole | 65277-42-1 |
| B0046-464063 | Terbinafine hydrochloride | 78628-80-5 |
| B0046-476797 | Itraconazole | 84625-61-6 |
| B0084-461995 | Micafungin sodium | 208538-73-2 |
| B0084-463563 | Efinaconazole | 164650-44-6 |
| B2695-127101 | Oligomycin A | 579-13-5 |
| B0084-467187 | Azoxystrobin | 131860-33-8 |
| B1370-158131 | Methyl rosmarinate | 99353-00-1 |
| B2693-470198 | DIMBOA | 15893-52-4 |
| B0046-463837 | Voriconazole | 137234-62-9 |
| B2693-205645 | Atpenin A5 | 119509-24-9 |
| B0084-284860 | Loflucarban | 790-69-2 |
| B2695-301717 | Griseofulvin | 126-07-8 |
| B2695-313998 | Rezafungin | 1396640-59-7 |
| B0084-333626 | Ciclopirox | 29342-05-0 |
| B0084-335900 | Fluconazole | 86386-73-4 |
| B1370-381786 | Protoneogracillin | 191334-50-6 |
| B0084-400393 | Terconazole | 67915-31-5 |
| B1370-449820 | Penetratin Trifluoroacetate |