2.2.3. Azoles.
Its mode of action, therapeutic properties, and resistance mechanisms developed by fungi and also by pharmaceutical companies, who get involve in enhancing its efficacy studied more. Hence it is mostly used antifungal agent in clinical practice. Azoles are two types i.e. imidazoles contain two nitrogen atoms, and the triazoles contain three nitrogen atoms which was classified according to number of nitrogen atoms presents in this cyclic organic molecules.
Azole drugs target the key enzyme i.e. the lanosterol 14-alpha demethylase, encoded by ERG11 gene. This inhibition occurs through the binding of the free nitrogen atom of the azole ring to the iron atom of the heme group of the enzyme. That leads to the synthesis of toxic compounds, which are unable to successfully replace ergosterol.
In 1958, scientific community consider azoles as potential antifungal agents but it was first synthesized in 1944 by Woolley. Later aprrox late 1960, clotrimazole, econazole, and miconazole was also introduce for treatment. However, their use was …show more content…
This agents mainly target (1,3)-b-D-glucan synthase which plays an important role in the synthesis of cell wall component of pathogenic fungi such as Candida spp. and Fusarium spp. That leads to disruption of the growing cell wall structure, resulting in osmotic instability and death of susceptible yeast cells. The target of echinocandins was not present in mammalian cells, so there is minimum toxicity of drug. There is an activating and a catalytic subunit of β (1-3)-glucan synthase encoded by FKS genes. Two FKS genes (FKS1 is expressed during the vegetative growth phase and FKS2 during sporulation) are found within the genome in most of fungi [P. Mazur et.al, 1995]. This therapeutic drug is able to inhibit both isoforms of the enzyme [N. H. Georgopapadakou,
Its mode of action, therapeutic properties, and resistance mechanisms developed by fungi and also by pharmaceutical companies, who get involve in enhancing its efficacy studied more. Hence it is mostly used antifungal agent in clinical practice. Azoles are two types i.e. imidazoles contain two nitrogen atoms, and the triazoles contain three nitrogen atoms which was classified according to number of nitrogen atoms presents in this cyclic organic molecules.
Azole drugs target the key enzyme i.e. the lanosterol 14-alpha demethylase, encoded by ERG11 gene. This inhibition occurs through the binding of the free nitrogen atom of the azole ring to the iron atom of the heme group of the enzyme. That leads to the synthesis of toxic compounds, which are unable to successfully replace ergosterol.
In 1958, scientific community consider azoles as potential antifungal agents but it was first synthesized in 1944 by Woolley. Later aprrox late 1960, clotrimazole, econazole, and miconazole was also introduce for treatment. However, their use was …show more content…
This agents mainly target (1,3)-b-D-glucan synthase which plays an important role in the synthesis of cell wall component of pathogenic fungi such as Candida spp. and Fusarium spp. That leads to disruption of the growing cell wall structure, resulting in osmotic instability and death of susceptible yeast cells. The target of echinocandins was not present in mammalian cells, so there is minimum toxicity of drug. There is an activating and a catalytic subunit of β (1-3)-glucan synthase encoded by FKS genes. Two FKS genes (FKS1 is expressed during the vegetative growth phase and FKS2 during sporulation) are found within the genome in most of fungi [P. Mazur et.al, 1995]. This therapeutic drug is able to inhibit both isoforms of the enzyme [N. H. Georgopapadakou,