Nanoemulsion Improves the Antifungal Activity of Allylic Thiocyanates against Yeasts and Filamentous Pathogenic Fungi

Abstract

We report the antifungal and antichemotactic activities of a series of allylic thiocyanates with low toxicity. We also show improved antifungal activity of the most promising compound when used in a nanoemulsion (NE). The 4‐chlorophenyl‐substituted allylic thiocyanate (compound 11) exhibited a broad spectrum of antifungal activity and showed antichemotactic effects with 100% reduction in leucocyte migration. Minimal inhibitory concentrations ranged from 25 to 50 μg mL−1, and the mechanism of action was related to complexation with fungal ergosterol. The NE containing compound 11 enhanced the antifungal activity approximately 64‐fold for dermatophytes and 4‐fold for Candida spp.. Compound 11 was not mutagenic and did not cause cell death or significant haemoloysis, although it exhibited mild dose‐dependent DNA damage. It was not an irritant for chorioallantoic membrane of fertile white eggs and exhibited 100% inhibition of fungal growth in an in vivo model of dermatophytosis. Our data indicate that allylic thiocyanates are very promising for the antifungal potential in nanostructured systems, with associated anti‐inflammatory effect.

Design, synthesis, and evaluation of novel 2-substituted 1,4-benzenediol library as antimicrobial agents against clinically relevant pathogens

“…The rupture of the cell could be related to the effect of the molecule on the cell wall and consequent death of the microorganism (fungicidal effect). The same morphological damage in fungi cells was recently observed in related studies using SEM, after treating the strains with a variety of others organic compounds (Dalla Lana et al, 2015, Dalla Lana et al, 2018, Dalla Lana et al, 2019, Batista et al, 2017).…”

Allylic Selenocyanates as Antifungal Agents Against Pathogenic Candida Species

“…Based on these antimicrobial activity reports in the literature, our research groups began investigating compounds derived from organoselenocyanates with different structural modifications. The related allylic thiocyanates show antitubercular, antibacterial, and antifungal activity . In addition to allylic thiocyanates, allylic selenocyanates (AS) were synthesized and tested on Fusarium spp., although these molecules have not been studied on yeast‐like fungi.…”

Discovery of a novel and selective fungicide that targets fungal cell wall to treat dermatomycoses: 1,3‐bis(3,4‐dichlorophenoxy)propan‐2‐aminium chloride

“…The HET‐CAM is a sensitive assay to determine the irritation effect associated with topical use. Thus, this technique becomes an alternative to others in vivo . So, the compound 2j showed an appropriate score confirming its potential.…”

“…The MIC range for dermatophytes was 0.39‐3.12 µg/mL and for yeast was 0.78‐1.56 µg/mL, reinforcing the data from the screening that this compound is actually active at very low concentrations. In other studies, the presence of chlorine in chemical structures investigated as to the antifungal application has already been verified as determinant for effective activity . Structurally, the position of the chlorine is important for improving the antifungal action, since the substitution at positions meta and para of the disubstituted molecule 2j was more advantageous (lower MICs) than the substitution at ortho and para positions as for 2i (Figure ).…”

“…Cells were adhered in coverslips previously functionalised with poly‐ l ‐lysine for 1 hours. Adhered cells were dehydrated in a series of freshly made solutions of graded acetone 30%, 50%, 70%, 95% (5 minutes) and 100% (10 minutes) . Samples were then subjected to critical point drying (EM CPD 300; Leica), mounted on metallic stubs, sputter coated with a 15‐20 nm gold‐palladium layer and visualised in a scanning electron microscope (Carl Zeiss EVO‐MA10 Carl) operating at 10 kV.…”