# Cellular Entry, Cytotoxicityicity, and Antifungal Activity of Newly Synthesized Dendrimers
## 4 Discussion
### Antifungal Activities of DAB and DAB-Br  
Many polymers are known to exhibit antimicrobial activity, but much less attention is paid to their specific antifungal properties. The mechanisms underlying microbial cell death induced by various polymers include cytotoxicity mediated by reactive oxygen species (ROS), the disruption of the microbial cell envelope, and the inhibition of nucleic acid and protein synthesis. Polymers with antimicrobial activity often possess cationic surface groups, which facilitate electrostatic interactions with the negatively charged microbial membranes, leading to membrane destabilization and cell death [44]. [PERSON] et al. [45] explored the antibacterial and antifungal activities of polymeric materials concerning their structure-activity relationships and membrane-active mechanisms of action. The researchers demonstrated that cationic polymers effectively inactivated _Candida_ spp. and _Cryptococcus_ spp., achieving up to a 5-log reduction in viable cells compared to the control. These cationic polymer coatings act via a membrane-active mechanism, disrupting the lipid membranes of both bacterial and fungal cells. In a study by [PERSON] and [PERSON] [46] investigating the antifungal activity of antimicrobial peptides, several fungal cellular components were identified as primary targets, including the chitin-rich cell wall, the cell membrane, and various intracellular structures. Membrane-active antifungal peptides exert their effects through diverse mechanisms, such as cilium-like disruption, membrane thinning, aggregation, toroidal pore formation, and barrel-stave (barrelation) models of membrane penetration [46; 47]. Evidence in the literature shows that dendrimers share a similar mode of action to cationic antimicrobial peptides [48; 49]. According to recent findings, the antifungal activity of dendrimers includes four main mechanisms [18]:  
1. Electrostatic interaction between the cationic terminal groups of the dendrimer and the anionic cell membranes, leading to an increase in membrane permeability;
2. A \"carpet\" mechanism in which dendrimers form small pores in the cell membrane, compromising membrane integrity and membrane repair mechanisms;
3. Inhibition of 1,3-\(\beta\)-D-glucan synthase, which disrupts cell wall synthesis and leads to leakage of cellular components;
4. Chelation, by which microbial enzymes are inhibited. The degree of dendrimer toxicity is influenced by both their concentration and the presence of positively charged functional groups. Higher concentrations of antimicrobial compounds generally enhance their ability to inhibit fungal growth. In addition, several other physicochemical properties, such as molecular structure, dipole moment, solubility, molecular geometry, and electrical conductivity, also contribute significantly to their antifungal activity [50]. Anionic and neutral dendrimers are less toxic to fungal cells than cationic ones. Studies of the antifungal activity of cationic dendrimers suggest an interaction with the negatively charged cell membrane, leading to pore formation, increased permeability, and impaired membrane integrity. As a result, membrane depolarization can be induced and ultimately collapse and dead cells. Moreover, dendrimers may penetrate into the cell and may affect organelles and vital cell processes [51; 52; 53]. Our investigation of the antifungal activity of DAB and DAB-Br demonstrated potent inhibitory effects against all five fungal strains (_Asp. fumigatus, Alt. alternata, Asp. niger, P. griseofuluum_, and _C. albicans_) with their effectiveness being both time- and concentration-dependent. DAB-Br showed greater antifungal potency than DAB. Notably, DAB-Br achieved complete growth inhibition of all tested fungal strains at a lower minimum inhibitory concentration (0.148 \(\mathrm{\SIUnitSymbolMicro\SIUnitSymbolMicro\SIUnitSymbolMicro  
tested concentration of both dendrimers (0.0369 \(\upmu\)g/uL). The stronger antifungal activity of DAB-Br is attributed to the bromine atom in the dendrimer structure.