Chapter 6 Antifungal Drugs
Classification by structural type: antibiotics, azoles, other classes
Section 1 Azole Antifungal Drugs
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1. Classification: imidazole
2. Mechanism of action:
Inhibits fungal cytochrome P-450, inducing changes in cell permeability and cell death.
3. Commonly used drugs
1. Miconazole nitrate
Imidazole class
Chemical name: 1-[2-(2 , 4-dichlorophenyl)-2-[(2,4-dichlorophenyl)methoxy]ethyl]-1H-imidazole nitrate
Deep infection, broad spectrum
2. Ketoconazole
Chemical name: cis-1-acetyl-4-[4-[2-(2,4-dichlorophenyl)-2(1H-imidazole-1 -Methyl)-1,3-dioxolane-4-methoxy]phenyl]-piperazine
It is hepatotoxic
In addition to being antifungal, it can reduce serum Testosterone levels, treatment of prostate cancer
3. Fluconazole
Chemical name: α-(2,4-difluorophenyl)-α-(1H-1,2, 4Triazol-1-ylmethyl)1H1,2,4triazol-1-ylethanol.
Features: High oral bioavailability, can penetrate the central nervous system, and has antifungal spectrum.
4. Clotrimazole
Structural characteristics: Tritylimidazole, highly toxic, mostly used externally.
5. Itraconazole
4. Structure-activity relationship of azole antifungal drugs
1. The nitrogen-containing azole ring is necessary, and the triazole activity Stronger
2. The substituent connected to the 1-position of the azole ring
3. When Ar is a benzene ring, there is an electronegative substituent at the 4-position or 2-position
(Halogen) has good activity
4. R1 and R2 change greatly, and dioxolane (ketoconazole) has the best activity and high toxicity, so it is preferred for external use.
R1 is an alcohol (fluconazole), the first choice for deep parts
5. There are stereochemical requirements
Section 2 Other categories
1. Terbinafine
Features: naphthalene, allylamine, alkyne
Broad spectrum
Treatment of superficial fungal infections
2 . Flucytosine
1. Best choice question
1. Which of the following does not conform to the structure-activity relationship of quinolone drugs
A. The substituent at position 1 is The antibacterial activity is enhanced when cyclopropyl is used
B. The activity is increased when there is an alkyl substitution at position 5
C. Carboxyl group at position 3 and ketone group at position 4 are necessary pharmacophore groups
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D. F substitution at position 6 can enhance cell permeability
E. Piperazine substitution at position 7 can enhance antibacterial activity
Answer: B
II. Compatibility Multiple Choice Questions
A. Isoniazid
B. Terbinafol
C. Norfloxacin
D. Flucytosine
E. Ethambutol
1. Easily soluble in acetic acid, hydrochloric acid or sodium hydroxide solution
2. Forms a red chelate with copper ions
3. It is an allylamine antifungal drug
4. Reacts with CuSO4 test solution and turns dark blue under alkaline conditions
Answer: 1.C 2.A 3.B 4.E
3. Multiple-choice questions
6. What is a drug with an acid-base structure? /p>
A. Para-aminosalicylic acid
B. Trimethoprim
C. Rifampicin
D. Levofloxacin
p>E. Sulfamethazole
Answer: ADE