In this lecture, we discuss the Antifungal Drugs – Mechanism of Action (PART-1)
Hi friends today in this lecture we are going to look at the anti-fungal agents anti-fungal agents are the special class of drugs which are designed to treat mycosis or fungal infections and these anti-fungal agents they work either through fungus static action meaning that they are going to inhibit fungal growth or they work either through fungicidal action
Meaning that they are going to kill the fungi now let’s draw a simplified fungal cell with a cell wall cell membrane and nucleus and these three compartments called cell wall cell membrane and nucleus these three compartments are acting as the targets of anti-fungal agents so different groups of antifungal drugs targets these different compartments for example
Glucan synthesis inhibitors targets the cell wall dna and rna synthesis inhibitors and mitosis inhibitors they are going to target the nucleic acids or nucleus and lastly cell membrane has become the target of ergo sterile synthesis inhibitors which includes azules and olalla means and the cell membrane disruptors which includes polyenes definitely one of the
Things that we want to study off antifungals is their mechanism of action so in this first part of lecture we are going to focus only on the mechanism of action of all the antifungal drugs right now if you look at the picture here you find that fungal cell is made of of outer cell wall and inner cell membrane and cell membrane is mostly made of phospholipids and
With some sterile molecules called air gossett iran and the most common target and antifungal drugs is the membrane sterile component called a ergosterol so you are thinking what do you mean by ergo steer on say similar to mammalian cholesterol air ghost it all is the fungal cholesterol that is found in fungal cell membrane which acts to maintain cell membrane
Stability or integrity so without air goes tear on the structure of the cell membrane is going to disrupt and this will cause membrane-bound proteins called ion channels stopped working properly and this will also make the cell membrane so frozen which eventually leads to inhibition of fungal growth if you see here this is the synthesis pathway of argus tear
On the precursor of both mammalian cholesterol and fungal air ghost it all is lanister on and the precursor of lanosterol is squaring and if you see here the conversion of squalene to lanosterol is going to happen via the formation of square in epoxide and this whole thing is catalyzed by an enzyme called squalene epoch series see fungi have a cytochrome p450
Enzyme called 14 alpha demethylase enzyme in the mitochondria as well as in the endoplasmic reticulum and do you know what is the speciality of this enzyme see this enzyme is going to convert lanosterol to air ghost arrow as i said earlier it’s worth to repeat it again without air ghost arrow on the structure of the cell membrane is going to be disrupt and this
Will cause membrane-bound proteins like ion channels stopped working properly and the membrane is going to become fragile which eventually leads to inhibition of fungal growth there is a group of drugs called polyenes which include amphotericin b and nice study and these poly ins are designed in such a manner that these drugs are going to bind to a ghost iran
And by binding to ergosterol they’re actually going formed some artificial pores in the cell membrane thereby making the cell membrane of fungi very permeable or very leaky and this causes significant changes in the ion balance including the loss of intracellular potassium and this leads to the death of fungal cell if you go step back in the synthesis pathway
You can see that target that some other group of drugs works on there is a group of antifungal drugs called as holes that can inhibit the enzyme called 14 alpha demethylase by inhibiting this enzyme you are going to block the conversion of lanister all – ergo stearin so these class of drugs called as holes they are going to inhibit the synthesis of air cos you’re
On remember never just memorize the drug name and the enzyme that it inhibits but you need to know the pathway that while you are on a drug like azoles for example fluconazole you are going to accumulate lanosterol because you are not going to form a ghost at all and this inhibition of the formation of a ghost iran is going to disrupt the membrane thereby the
Fungal cell dies now if you back up much earlier in that whole synthesis pathway you see the target where the drug called terbinafine is going to works on it blocks an enzyme called squalene eep oxidase that’s an enzyme that converts squalene into squaring epoxide eventually this will inhibit the production of ergo sterile as well but the specific action of
Terbinafine results in the accumulation of square e which is toxic to the fungus and this concludes our antifungal targets in the cell membrane now let’s discuss our antifungal targets in the cell wall as i said earlier fungal cell is made of a strong outer cell wall and inner cell membrane and this tough outer cell wall is made of carbohydrate molecules the
Question is what makes this fungal cell wall to be so strong do you think it’s just the presence of carbohydrate molecules in the cell what is going to make strong the answer is no see some fungal species how beta glucans which are polysaccharide polymers that are cross linked with other carbohydrate molecules to make a strong cell wall do you know how this beta
Glucans are produced see these beta glucans are produced by an enzyme called beta 1 3 glucan synthase and this enzyme is not found in human cells which makes it a good target for antifungal medications see there is a group of antifungal drugs that specially target this beta 1 3 glucan synthase enzyme and these class of drugs are called a kind of tandon’s or we
Call it as funding drugs these fungi in trucks include any jula fungal mica fungal and kasbah fungus where these drugs are going to inhibit the synthesis of a cell wall component called beta glucan thereby it’s going to prevent the formation of beta glucan thereby it prevents the cross-linking of carbohydrate molecules and it makes the cell wall so fragile so
Up to now we have discussed only the mechanism of action of drugs that targets two cell wall as well as cell membrane compartments now let’s move to the drugs that interact with nucleus compartment see these drugs include microtubule function inhibitors and nucleic acid synthesis inhibitors like dna and rna synthesis inhibitors as well as mitosis inhibitors
See there is a drug called griseofulvin which interferes with mitosis by attacking microtubules you know microtubules are vital for mitosis so by attacking the microtubules brisky of alveen is going to effectively prevents the fungus from replica there is a drug called flu cytosine or five-floor of cytosine or simply you can say it as phi fc in short and this
So-called flu cytosine is converted to 5-fluorouracil or phi fu in short by a special type of fungal enzyme called fungal cytosine deaminase enzyme say you recognize 5-fluorouracil as an anti-cancer drug in other words if you understand the mechanism for flu cytosine or phi fc you also know the mechanism for 5-fluorouracil c 5-fluorouracil forms v flora deoxy
You read in mono phosphate which is abbreviated to phi f dump in short now what does this 5 floridi oxygen mono phosphate is going to compete with this so-called phi f dump is going to compete with deoxy you reading mono phosphate for the enzyme time-delayed synthase so these drugs inhibit time we delayed synthase an enzyme that converts deoxy you read in mono
Phosphate into deoxy time eating mono phosphate so when you give this drug called flu cytosine or v fluoro cytosine or 5-fluorouracil then these cells they can’t form thymine therefore fungal cells stop producing dna and rna and this leads to death of fungi so my dear friends this is all about the mechanism of action of anti-fungal agents in the next part we go
Into detail of each class of anti-fungal agents and we discussed in detail about the remaining aspects of this class of drugs right so we meet in the next lecture till then stay tuned have a nice day
Transcribed from video
Antifungal Drugs Part 1 – MECHANISM OF ACTION (MOA) | Made EASY By Concept Clear