Photosensitizers Mediated Photodynamic Inactivation against Fungi

Abstract

Superficial and systemic fungal infections are essential problems for the modern health care system. One of the challenges is the growing resistance of fungi to classic antifungals and the constantly increasing cost of therapy. These factors force the scientific world to intensify the search for alternative and more effective methods of treatment. This paper presents an overview of new fungal inactivation methods using Photodynamic Antimicrobial Chemotherapy (PACT). The results of research on compounds from the groups of phenothiazines, xanthanes, porphyrins, chlorins, porphyrazines, and phthalocyanines are presented. An intensive search for a photosensitizer with excellent properties is currently underway. The formulation based on the existing ones is also developed by combining them with nanoparticles and common antifungal therapy. Numerous studies indicate that fungi do not form any specific defense mechanism against PACT, which deems it a promising therapeutic alternative.

Keywords: fungi; infections; macrocycle; photocytotoxicity; photodynamic therapy.

Figure 1

Structure of fungi cell wall.

Figure 2

Mechanisms of fungal resistance: (A) The development of new mechanisms by fungi, which are no longer a target for antifungals. (B) Limiting the penetration of substances from the outside of the matrix. (C) Breakdown of antifungals by enzymes. (D) Changing the molecular target. (E) Pumping out molecules from the inside of the cell.

Figure 3

Chemical structures of (1–8).

Figure 4

Chemical structures of (9–13).

Figure 5

Chemical structure of 14–16.

Figure 6

Chemical structures of 17–21.

Figure 7

Chemical structures of 22–26.

Figure 8

Structures of chlorins (27–32).

Figure 9

Chemical structures of chlorins (33–38).

Figure 10

Chemical structures of (39–46).

Figure 11

Chemical structures of (47–57).

Figure 12

Chemical structures of 58–71.

Figure 13

Conclusions in brief.