PPH 308: MEDICINAL CHEMISTRY-II

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PPH 308: MEDICINAL CHEMISTRY – II Unit: IV: Antifungal agents

Antifungal agents: Synthesis of Griseofulvin, Fluconazole.

– Fungal infections are caused by microscopic organisms that can invade the epithelial tissue.
– The fungal kingdom includes yeasts, molds, rusts and mushrooms. Fungi, like animals, are hetrotrophic, that is,

they obtain nutrients from the environment, not from endogenous sources (like plants with photosynthesis).
– Most fungi are beneficial and are involved in biodegradation; however, a few can cause opportunistic infections if

they are introduced into the skin through wounds, or into the lungs and nasal passages if inhaled.
– Diseases caused by fungi include superficial infections of the skin by dermatophytes in the Microsporum,

Trichophyton or Epidermophyton genera. These dermophytic infections are named for the site of infection rather
than the causative organism.

Dermophytic Infection Causative Organism

Tinea corporis (ringworm) Microsporum canis, Trichophyton mentagrophytes

Tinea pedis (athlete’s foot) T. rubrum, T. mentagrophytes, Epidermophyton floccosum

Tinea cruis (jock itch) T. rubrum, T. mentagrophytes, E. floccosum

Tinea capis (scalp) M. canis T. tonsurans

Tinea barbae (beard/hair) T. rubrum, T. mentagrophytes

Tinea unguium (nails) T. rubrum, T. mentagrophytes, E. floccosum

– Systemic infections are caused by the inhalation of spores and cause fungal pneumonia. This pneumonia cannot be
transmitted from human to human. These infections can occur in otherwise healthy individuals. Many of the
organisms that cause systemic fungal infections are confined to specific geographic locations due to favorable
climates for their proliferation.

Systemic Infections Causative Organism Geographic Location

Coccidioidomycosis Cocidioides immitis Southwestern U.S. and parts of Latin America

Histoplasmosis Histoplasma capsulatum Central and Eastern U.S

Brazilian Blastomycosis Paracoccidioides brasiliensis South America

Blastomycosis Blastomyces dermatitidis Southeastern U.S. and Mississippi River valley

– Organisms that cause opportunistic infections will not gain a foothold in healthy individuals, but in the
immunocompromised they can cause serious, sometimes life-threatening infections. Patients especially susceptible
to these infections include individuals with leukemia and other blood diseases, cancer, HIV and other
immunodeficiencies, and diabetes. These organisms can be found throughout the U.S.

Systemic Infections Causative Organism Geographic Location

Candidaisis, Thrush, Vulvovaginitis Candida albicans GI tract and vagina

Through inhalation, may cause mild
Cryptococcal meningitis Cryptococcus neoformans

lung infection. Mainly affects CNS

Aspergillosis Aspergillus sp. Lung, brain, sinuses and other organs

Mucormycosis Murcor sp. Sinuses, eyes, blood and brain

Lungs (especially prevalent in HIV
Pneumocystis carinii pneumonia Pneumocystis carinii

patients)

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Lecturer Notes_Dr. S. Mondal_B. Pharm 6 Semester_GITAM (Deemed to be University) Page | 1
E-mail: [email protected]

PPH 308: MEDICINAL CHEMISTRY – II Unit: IV: Antifungal agents

 Chemical Classification of Anti-fungal agents

Antibiotics Amphotericin B, Nystatin, Griseofulvin

Triazoles Fluconazole, Itraconzole, Terconazole

Imidazoles Clotrimazole, Ketoconazole, Miconazole, Bifonazole, Butoconazole, Zinoconazole

Fluorinated pyrimidines Flucytosine

Chitin synthetase inhibitors Nikomycin Z

Peptides/proteins Cispentacin

Miscellaneous Ciclopirox, Tolnaftate, Naftifine, and Terbinafine

Griseofulvin Fluconazole

Clotrimazole Flucytosine

Nikomycin Z Cispentacin

Ciclopirox

 Classification Based on the Route of Administration

– Drugs for subcutaneous and systemic mycoses: Amphotericin B, Fluconazole, Flucytosine, Itraconazole,
Ketoconazole.

– Drugs for superficial mycoses: Clotrimazole, Econazole, Griseofluvin, Miconazole, Nystatin.

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Lecturer Notes_Dr. S. Mondal_B. Pharm 6 Semester_GITAM (Deemed to be University) Page | 2
E-mail: [email protected]

PPH 308: MEDICINAL CHEMISTRY – II Unit: IV: Antifungal agents

 Griseofulvin

 Synthesis

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Lecturer Notes_Dr. S. Mondal_B. Pharm 6 Semester_GITAM (Deemed to be University) Page | 3
E-mail: [email protected]

PPH 308: MEDICINAL CHEMISTRY – II Unit: IV: Antifungal agents

 Mode of action

– Griseofulvin is a fungi-static drug that causes disruption of the mitotic spindle by interacting with polymerized
microtubules.

 Dose

– As an oral suspension, the administered dose is 125 mg/5 ml; as capsules, 250 or 500 mg as tablets. For adults, in
divided doses, the dose is 500 mg/day.

 General Mechanism action of Antifungal agents

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Lecturer Notes_Dr. S. Mondal_B. Pharm 6 Semester_GITAM (Deemed to be University) Page | 4
E-mail: [email protected]

PPH 308: MEDICINAL CHEMISTRY – II Unit: IV: Antifungal agents

 Fluconazole

 Synthesis

 Dose

– The administered dose for superfi cial mucosal candidiasis for adults is 50 mg daily, which is increased to 100 mg
daily.

– Recommended treatment duration is 7–14 days; in the case of oropharyngeal candidiasis, 14 days for atrophic oral
candidiasis associated with dentures, 14–30 days for other mucosal candidal infections, including oesophagitis.

– In the case of children, more than 4 weeks the loading dose is 6 mg/kg followed by 3 mg/kg daily.
– The administered dose for dermatophytosis, pityriasis versicolor, and candida infections for adults is 50 mg daily

for up to 6 weeks.

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Lecturer Notes_Dr. S. Mondal_B. Pharm 6 Semester_GITAM (Deemed to be University) Page | 5
E-mail: [email protected]

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