Medicinal Chemistry-III

Unit 4
Part-1: Antifungal Agents
These are the agents which are used in treatment of fungal infections. These agents kill or arrest
growth of fungi topically or systemically.

Human-fungi parasitic relationship leads to mycotic illnesses or mycosis (superficial fungal infection on
skin or mucous membranes). It can be controlled by local application of antifungal agents.

Fungi’s cell wall contains chitin instead of peptidoglycan & cell membrane contains ergosterol &
lanosterol.

Classification of Antifungal agents:

Drugs MOA & Uses

I. Antibiotics
(1) Amphotericin B Binds with ergosterol present in fungal cell
membrane & form pores or channels
Obtained from Streptomyces nodosus causing leakage of small molecules such as
K+, Na+, Mg2+ sugars etc. leading to cell
death
Treat topical fungal, yeast infection, vulvo-
vaginal infection.

(2) Nystatin Same as Amphotericin B

Obtained from Streptomyces noursei

(3) Natamycin Binds to ergosterol present in fungal cell

membrane & prevent sterol synthesis,
amino acid & glucose transport.
Treat fungal infections of eyelids,
conjunctiva & cornea, preservative in food
industry.
 (4) Griseofulvin Fungi-static agent causing mitotic spindle
disruption with polymerized
microtubules, inhibit cell wall synthesis
Treat superficial infection caused by
trichophytes, treat ringworm infection of
skin, hair & nails

II. Synthetic Antifungal Agents

A. Azoles Inhibit sterol 14-α-demethylase,
microsomal cytochrome P450 dependent
enzyme system & thus impair ergosterol
biosynthesis & decrease cell wall rigidity 
cell lysis  cell death. It leads to
accumulation of 14-α-methyl sterols. These
sterols may disrupt packing of aryl chains
of phospholipids, ATPase & enzymes of
electron transport system, thus inhibiting
fungal growth.
a) Imidazoles
(1) Clotrimazole Treat topical fungal, yeast infection, vulvo-
vaginal infection.

(2) Miconazole Active against Candida spp.

(3) Econazole Treat athlete’s foot, jock itch & ring worm

(4) Butoconazole
(5) Oxiconazole Treat athlete’s foot, jock itch & ring worm

(6) Tioconazole

(7) Ketoconazole Active against Candida spp. & Cryptococcus

neoformans
Treat Cushing syndrome

b) Triazoles
(1) Fluconazole Fungistatic & Active against Candida spp. &
Cryptococcus spp.

(2) Itraconazole Treat fungal infections in immune

compromised & non-immune
compromised patients
Treat topical fungal, yeast infection, vulvo-
vaginal infection.

(3) Terconazole Active against Candida spp.

B. Miscellaneous
(1) Naftifine HCl Fungicidal activity against Tinea cruris &
Corporis spp.
 Inhibits squalene-2,3-epoxidase & inhibits
fungal biosynthesis of ergosterol

(2) Tolnaftate Active against Microsporum canis

Synthesis:

1. Miconazole

2. Tolnaftate