This document discusses several antifungal drugs including natamycin, clotrimazole, miconazole, ketoconazole, fluconazole, tolnaftate and their mechanisms of action, uses, and common adverse effects. It also covers the structural requirements and mechanisms of action of azole antifungals.

11. Obtained from Streptomyces nodosus
These drugs are most activeat pH6- 7.5)

16. Natamycin (pimaricin)
It is a amphoteric macrolide antifungal antibiotic obtained from
streptomyces natelensis
Used topically for the treatment of variety of fungal infections.
It exert its effect by binding to sterol in the fungal cell thereby
increasing the membrane permeability, this leads to leakage and
loss of essential constituents

17. Obtained from Penicillium griseoflavium
Thus inhibits nucleic acid
synthesis

21. Allylamine: Terbinafine
Used in treatment of Dermatophytosis
Adverse effects:-gastric upset, rashes and
taste disturbances
Rarely hepatotoxicity
Naftifine

25.  Clotrimazole is a broad-spectrum fungistatic imidazole drug used in the
topical treatment of oral, skin, and vaginal infections with Candida.
albicans.
 It is also employed in the treatment of infections with cutaneous
dermatophytes.
Miconazole is used in the treatment of vaginal infection
 Miconazole is used to treat skin infections such as athlete's foot, ringworm, and
other fungal skin infections (candidiasis). This medication is also used to treat a skin
condition known as pityriasis (tinea versicolor), a fungal infection that causes a
lightening or darkening of the skin of the neck, chest, arms, or legs.
Adverse effect
Burning
Itching
Nausea
Vomiting

26. Econazole
Butaconazole

27. Tioconazole

29. Used to treat fungal infections of
toe,nails,mouth and lungs

30. Adverse effect(KETOCONAZOLE)
 Nausea, vomiting and anorexia occur
commonly but these adverse effects can
be minimized by taking ketoconazole with
food
 Allergic dermatitis
 inhibits the synthesis of testosterone and
estradiol which may lead to
gynaecomastia and irregular menstrual
cycles

31. FLUCONAZOLE
Used to treat fungal infections of
toe,nails,mouth and lungs
Terconazole

32. OXYCONAZOLE
Used to treat
infections such as
athlets foot, ring
worm infections

33. The basic structural requirments for the
member of azoles is a weakly basic imidazole or
1,2,4triazole ring (pKa of 6.5–6.8) bonded by
nitrogen carbon linkage to rest of the molecule
SAR of azoles

34. The amidine nitrogen atom (N-3 in the
imidazoles, N-4 in the triazoles) bind to the
heme ion of enzyme bound cytochrome
P450 prevent the oxidation of steroidal
substance by enzyme
The enzyme is also present in mammalian
biosynthesis of cholesterol and mammalian
copy of the enzyme is much sensitive and
binds to azoles, so Imidazole ring can be
replaced with 1,2,4-triazole ring ( binds
with lower affinity to mammalian copy of
demethylase)

35.  The most potent antifungal azoles
possess two or three aromatic
rings, at least one of which is
halogen substituted

36.  The most potent halogen is fluorine,
although other groups like sulfonic
acids do the same
 Only 2, and/or 2,4 substitution yields
effective azole compounds
 Substitution at other positions of the
ring yields inactive compounds
 large nonpolar portion of the
molecule mimics the nonpolar
steroidal part of the substrate for
lanosterol
 The non polar functional group
provide high lipophilicity to the
antifungal azoles

37. The free bases are typically insoluble
in water but soluble in organic
solvents like ethanol
Fluconazole which posses two
triazole moiety is an exceptional in
that it is sufficiently soluble in water
and injected intravenously
Fluconazole

38. Tolnaftate is used to treat fungal conditions
such as athlete's foot and ringworm.
Adverse effect
difficult breathing; swelling of face, lips,
tongue, or throat.
Miscellaneous

39. Thiocarbonyl chloride

40. Sodium caprylate
Zinc propionate