Antifungal antibiotics by M S holkar

1. Ms. Mandakini Sampat Holkar
(M.Pharm)
Dept. of Pharmaceutics
Shri Vithal Education and Reserch Institute’s
College of Pharmacy, Pandharpur

2. Biochemical targets for antifungal chemotherapy
Antifungal chemotherapy depends up on biochemical
differences between fungi and mammals
Most relevant difference between fungal and mammalian
cells is that cell membranes of fungi and mammalian
contain different sterols.
Sterol are important components of fungal and mammalian
cell membranes to proper functioning of cell membrane
enzymes and ion transport protein
Mammalian cell membrane contain- Cholesterol
Fungi contain- Ergosterol

3. Fungus cell membrane structure

5. Ergosterol biosynthesis from Squalene
Squalene Squalene
epoxide
Lanosterol
Ergosterol
Squalene
epoxidase
CYP 45014-alpha
demethylase

6. Classification of Anti-fungal drugs
1.Antibiotics-
A. Polynes- e.g. Amphotericin B, Nystatin,Natamycin
B. Heterocyclic benzofuran- e.g. Griseofulvin
2. Anti-metabolite- e.g.Flucytosine
3.Azoles-
A. Imidazole- (Topical)-e.g. Clotrimazole, econazole,
miconazole,oxiconazole
Systemic-e.g. Ketoconazole
B. Triazoles-(Systemic)-e.g. Fluconazole, itraconazole
C. Allyl amine - Terbinafine ,Naftifine
D. Other Topical agents - e.g.Undecylenic acid

7. Site of action of common antifungal drugs
Ergosterol
Lanosterol
Squalene
DNA
Ergosterol-rich fungal cell membrane
Terbinafine
Azoles
Flucytosine
Griseofulvin
Amphotericin
fungal cell wall
Microtubules

8. Polyene
Membrane distrupters- Nystatin,
Amphotericin B

9. Mechanism of action-
Polynes have higher
affinity for ergosterol
containing membranes
Leaky membrane
Insert in to
membranes disrupt
membrane function
Cell death
Loss of essential cell
constituents such as
ions

10. Nystatin

11. Uses-
• First clinically useful polyene antifungal antibiotic isolated from
bacterium streptomyces nouresei in 1951
•It is used to treat Candida infections of the skin including diaper
rash, thrush, esophageal candidiasis, and vaginal yeast infections
•Nystatin may be used by mouth, in the vagina, or applied to the
skin

12. Amphotericin B

13. Uses-
Amphotericin B was isolated from Streptomyces nodosus in 1955
and came into medical use in 1958
Amphotericin B is an antifungal medication used for serious
fungal infections and leishmaniasis
The fungal infections it is used to treat include aspergillosis,
blastomycosis, candidiasis, coccidioidomycosis, and cryptococcosis
mphotericin B is used for life threatening protozoan infections such
as visceral leishmaniasis[10] and primary amoebic
meningoencephalitis.

14. Griseofulvin
Griseofulvin was discovered in 1939 from a type of Penicillium
mold.
Griseofulvin is an antifungal medication used to treat a number
of types of dermatophytoses (ringworm). This includes fungal
infections of the nails and scalp, as well as the skin when
antifungal creams have not worked.It is taken by mouth.
Griseofulvin is used orally only for dermatophytosis. It is
ineffective topically. It is reserved for cases with nail, hair, or large
body surface involvement

15. Mechanism of action
binding to the
protein tubulin
Interferes with
function of
miotic spindle
It also
interferes with
DNA
replication
Inhibit cell
division
Griseofulvin

16. Flucytosine
Flucytosine by mouth is used for the treatment of serious
infections caused by susceptible strains of Candida or
Cryptococcus neoformans.
It can also be used for the treatment of chromomycosis
(chromoblastomycosis), if susceptible strains cause the
infection.

17. Flucytosine
is prodrug
Inhibit Protein
& RNA
biosynthesis
Inhibit
thymidylate
synthetase
Intrafungally
converted into
cytostatic
5- flurouracil
Mechanism of action
Fungal cytosine
deaminase
5-Fluorodeoxyuridine

18. Ergosterol biosynthesis
Inhibitors-Azoles

19. Mechanism of action-
Responsible for
converting lanosterol
to ergo sterol
Interfer with action
of membrane
associated enzyme
Alter the
fluidity of
membrane
Depletion of
ergo sterol
Azoles inhibit fungal CYP-
450 enzyme,14-alpha
demethylase
Azoles are a group of synthetic fungistatic agents with a broad
spectrum of activity based on the imidazole or triazole nucleus.
Net effect no
replication

20. Clotrimazole
Clotrimazole, sold under the brand name Canesten
among others, is an antifungal medication.
It is used to treat vaginal yeast infections, oral
thrush, diaper rash, pityriasis versicolor, and types of
ringworm including athlete's foot and jock itch.
It can be taken by mouth or applied as a cream to
the skin or in the vagina

21. Econazole
Econazole is used as a cream to treat skin infections such
as athlete's foot, tinea, pityriasis versicolor, ringworm,
and jock itch.
It is also sold in Canada under the brand name Ecostatin
as vaginal ovules to treat vaginal thrush.
Econazole nitrate exhibits strong anti-feeding properties
against the keratin-digesting common clothes moth
Tineola bisselliella

22. miconazole oxiconazole
Miconazole, sold under the brand name Monistat
among others, is an antifungal medication used to
treat ring worm, pityriasis versicolor, and yeast
infections of the skin or vagina.It is used for ring
worm of the body, groin (jock itch), and feet
(athlete's foot). It is applied to the skin or vagina as
a cream or ointment.
Oxiconazole (trade names Oxistat in the US,
Oxizole in Canada) is an antifungal medication
typically administered in a cream or lotion to
treat skin infections, such as athlete's foot,
jock itch and ringworm. It can also be
prescribed to treat the skin rash known as
tinea versicolor, caused by systemic yeast
overgrowth

23. Ketoconazole
Topically administered ketoconazole is usually prescribed for fungal infections
of the skin and mucous membranes, such as athlete's foot, ringworm,
candidiasis (yeast infection or thrush), jock itch, and tinea versicolor.
Topical ketoconazole is also used as a treatment for dandruff

24. Fluconazole,
Fluconazole is a first-generation triazole antifungal medication.
It differs from earlier azole antifungals (such as ketoconazole)
in that its structure contains a triazole ring instead of an
imidazole ring.
Fluconazole's spectrum of activity includes most Candida
species (but not Candida krusei or Candida glabrata),
Cryptococcus neoformans, some dimorphic fungi, and
dermatophytes, among others. Common uses include:
The treatment of non-systemic Candida infections of the
vagina ("yeast infections"), throat, and mouth.
Certain systemic Candida infections in people with healthy
immune systems, including infections of the bloodstream,
kidney, or joints.

25. Itraconazole
Itraconazole has a broader spectrum of activity than
fluconazole (but not as broad as voriconazole or
posaconazole). In particular, it is active against
Aspergillus, which fluconazole is not. It is also
licensed for use in blastomycosis, sporotrichosis,
histoplasmosis, and onychomycosis

26. Terbinafine
Squalene Squalene
epoxide
Lanosterol
Ergosterol
CYP 45014-alpha
demethylase
Squalene
epoxidase
Terbinafine
Accumulation
Squalene in cell
Toxic to cell

27. Terbinafine
.
Terbinafine is an antifungal medication that fights
infections caused by fungus.
Terbinafine tablets are used to treat infections
caused by fungus that affect the fingernails or
toenails.
Terbinafine oral granules are used to treat a fungal
infection of scalp hair follicles in children who are
at least 4 years old.

28. References-
Foye’s Principles of Medicinal chemistry fifth edition
Rang and Dale’s Pharmacology seventh edition
Link-
https://youtu.be/I9SiDPFMM3Y
https://youtu.be/T-dwE11AhqA
https://youtu.be/H11LP48mbTI
https://youtu.be/QcuPKy_Slng
https://youtu.be/uNvnGjpmnqI
https://youtu.be/QHlahl4FaqA