Antifungal drug development:

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Antifungal drug development The identification
of new targets
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?? Fungi ??? Mycology ????(Zygomycota)??
? ?????????????? ????(Ascomycota)??????
???????????? ????(Basidiomycota)???
????? ????????????,????? ?????(Deuteromyc
ota) ??????? ??????????????
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???????????? AIDS?? ?????? ?????? ?????
????
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Aspergillus sp. ?????? ????? Candida sp. ???
????? ?????
????? ?????? ????? Cryptococcus
neoformans ?????? Histoplasma capsulatum ????
Coccidioides immitis ?????? Blastomyces
dertum ?????? Paracoccidioides brasiliensis ?????
??????
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Antifungal strategies ????? ? Cell wall
glucan, chitin and mannoproteins
?????????????????? ? Cell membrane Ergosterol
vs cholesterol ?????? VS ??? ? Cytosol
target EF3 (elongation factor 3)
???????????3 ? define virulence factors
??????
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???????
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???????????? ?? polyene?????-Amphotericin
B
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?? azole?????????
Fluconazole
Itraconazole
???????DNA?RNA???
5-Fluorocytosine
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Cell wall 20-30 cell dry weight 50-60 glucan
( 5-10 b-1,6) 30-40 mannoproteins 40
different proteins 1-5 chitin
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Chitin (N-acetylglucosamine) n UDP- N-AG
n UDP (b-1,4- N-AG)n
n
b-1,4-N-acetylglucosamine polymer (chitin)
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Chitin synthase inhibitors
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b-1,3-Glucan (glucose polymer) b-1,3-glucan
synthase catalytic subunits FKS1 regulatory
subunits Rholp (GTP-GDP exchange)
b-1,3-glucan polymer
n
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glucan synthase inhibitors - cyclic
Aminohexapeptides
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????????? VS ????? ??? chitin synthase
inhibitor VS chitinase? ???? glucan
synthase inhibitor VS glucanase?
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New strategies? Combinations? amphotericin B,
azole 5-Fluorocytosine Impr
ovement diagnostic tools New drugs? Whats in
the pipeline?
5-Fluorocytosine
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