This presentation specially for the students of Bachelor of Pharmacy. It covers all the structures, mechanisms and few synthesis as per GTU syllabus.

1. Antifungal Agents
Prepared by:
Ms. Navdha Soni
Asst. Professor
L J Institute of Pharmacy

2. Introduction
§ Fungi are Eukaryotic cells.They possess mitochondria, nuclei & cell membranes.
§ They have rigid cell walls containing chitin as well as polysaccharides, and a cell
membrane composed of ergosterol.
§ While bacterial cells are prokaryotic. So, antibacterial agents can exhibit Selective
toxicity. In contrast, similarity between fungal & mammalian cells makes Antifungal
drugs nonselective.
§ Thus,Antifungal drugs are in general more toxic than antibacterial agents.
§ Depending upon some basic differences, fungi may be classified as
a. Phycomycetes (algae like),
b. Ascomycetes (sac like),
c. Basidiomycetes (mushrooms) &
d. Dueteromycetes 2

3. § Fungi that can cause infections live
⎯ In association with humans commensally
⎯ In Environment.
§ Fungal infections are termed as MYCOSES.
§ In the UK, the commonest fungal disease is
systemic Candidiasis.
Overview of fungal infection
3

4. Mycoses
Cutaneous Subcutaneos
Systemic mycoses due to
opportunistic pathagones
Systemic mycoses due to
primary pathagones
§ Cutaneous mycoses: These diseases are restricted to the keratinized layers of the skin,
hair, and nails.
§ Subcutaneous mycoses: It involve the dermis, subcutaneous tissues, muscle.These
infections are difficult to treat and may require surgical interventions such as
debridement.
§ Systemic mycoses due to opportunistic pathogens: Systemic mycoses due to
opportunistic pathogens are infections of patients with immune deficiencies who
would otherwise not be infected.
§ Systemic mycoses due to primary pathogens: Originate primarily in the lungs and
may spread to many organ systems
Clinical classifications of Mycoses
4

5. BiologicalTargets for AntifungalTherapy
§ Anti Fungal Therapy depends upon biochemical difference between fungal and
mammalian cell.
§ On cellular level fungal cell have cell wall where as mammal cell doesn’t have cell wall
so fungal cell is the target for those chemicals which inhibits cell wall synthesis.
§ Cell membrane of fungal cell contain different sterols which are essential for structure
of cell membrane.
§ Other target include inhibition of DNA biosynthesis , disruption of mycotic spindle
and interference of metabolism.
5

6. § Polyenes (Mostly antibiotics)
§ Azoles
⎯ Triazoles
⎯ Imidazoles
§ Fluorinated Pyrimidines
§ Natural Products
§ Chitin Synthetase Inhibitors
§ Peptide/Proteins
§ Miscellaneous Agents
Classification of Antifungal Agents
6

7. Amphotericin B
NystatinNatamycin
1.Polyenes
7

8. § Several amphotericin B molecules bind to
ergosterol in the plasma membranes of
sensitive fungal cells.
§ There, they form pores (channels) that
require hydrophobic interactions between
the lipophilic segment of the polyene
antibiotic and the sterol. The pores disrupt
membrane function, allowing electrolytes
(particularly potassium) and small
molecules to leak from the cell, resulting
in cell death.
§ Effective against various fungal infection
like aspergillosis, blastomycosis and
candida infection.
Mechanism of Action of Amphotericin B
8

9. 2.1 Triazoles:
Fluconazole Itraconazole
2.Azoles
9

10. § Fluconazole is a fluorine-substituted,
bis-triazole antifungal agent. Its
mechanism of action, like that of other
azoles, involves interruption of the
conversion of lanosterol to
ergosterol via binding to fungal
cytochrome P-450 and subsequent
disruption of fungal membranes.
§ Activity against Aspergillus spp.,
Blastomyces dermatitidis, Candida spp.,
Coccidioides immitis, Cryptococcus
neoformans, Histoplasma capsulatum,
and Paracoccidioides brasiliensis has
been demonstrated in several animal
models.
Ergosterol
LanosterolFluconazole
Mechanism of Action of Fluconazole
10

11. Clotrimazole Econazole Ketoconazole
2.Azoles
2.2 Imidazole:
11

12. Tioconazole Terconazole Miconazole
2.Azoles
2.2 Imidazole:
12

13. Butoconazole
Oxiconazole
§ Imidazole derivatives act by damaging
the fungal cell membrane.
§ They enhance the membrane
permeability by inhibiting the synthesis
of ergosterol which is primary cellular
sterol of fungi.
§ They are effective against superficial and
systemic infection.
2.Azoles
2.2 Imidazole:
13

14. Synthesis of
Miconazole
14

15. Flucytosine
§ The active metabolite is further
converted to 5-fluro-2’-deoxyuridylic
acid which interrupts the fungal DNA
synthesis by inhibiting thymidylate
synthetase enzyme.
§ Since, mammalian cells do not contain
cytosine deaminase, their function is not
affected by Flucytosine.
§ Besides this, it is also suspected to
interfere in protein synthesis.
3. Fluorinated Pyrimidines
15

16. Griseofulvin
4. Natural product
§ It is only fungistatic, and it causes a
number of significant drug interactions.
§ Griseofulvin accumulates in newly
synthesized, keratin-containing tissue,
where it causes disruption of the mitotic
spindle and inhibition of fungal mitosis.
16

17. Nikkomycin
§ Nikkomycin is found to be a potent growth
inhibitor of Candida albicans through
competitive inhibition of chitin synthase.
§ The activity of the peptide-nucleoside drug
has been antagonized by both peptone and
defined peptides. Transported dipeptides are
effective antagonists while transported
oligopeptides were not.
5. Chitin synthetase Inhibitor
17

18. Cispentacin
§ Cispentacin did not inhibit amino acid
biosynthesis in vivo but did elevate
levels of several amino acids possibly by
interfering with self-regulatory
mechanisms.
§ It is effective against Candida albicans
6. Peptide (Protein)
18
H2N
OHO

19. Benzoic Acid Salicylic Acid Nitroxoline
7. Miscellaneous Agents
19

20. Naftifine Tolnaftate
7. Miscellaneous Agents
20

21. SYNTHESIS
OF
TOLNAFTATE
21

22. THANK YOU