Carbonic anhydrase inhibitors. Inhibition and homology modeling studies of the fungal beta-carbonic anhydrase from Candida albicans with sulfonamides

Alessio Innocenti; Rebecca Hall; Christine Schlicker; Andrea Scozzafava; Clemens Steegborn; Fritz A Mühlschlegel; Claudiu T Supuran

doi:10.1016/j.bmc.2009.05.002

Carbonic anhydrase inhibitors. Inhibition and homology modeling studies of the fungal beta-carbonic anhydrase from Candida albicans with sulfonamides

Alessio Innocenti, Rebecca Hall, Christine Schlicker, Andrea Scozzafava, Clemens Steegborn, Fritz A Mühlschlegel, Claudiu T Supuran

Biosciences

Research output: Contribution to journal › Article › peer-review

52 Citations (Scopus)

Abstract

The beta-carbonic anhydrase (CA, EC 4.2.1.1) from the fungal pathogen Candida albicans (Nce103) is involved in a CO(2) sensing pathway critical for the pathogen life cycle and amenable to drug design studies. Herein we report an inhibition study of Nce103 with a library of sulfonamides and one sulfamate, showing that Nce103, similarly to the related enzyme from Cryptococcus neoformans Can2, is inhibited by these compounds with K(I)s in the range of 132 nM-7.6 microM. The best Nce103 inhibitors were acetazolamide, methazolamide, bromosulfanilamide, and 4-hydroxymethylbenzenesulfonamide (K(I)s

Original language	English
Pages (from-to)	4503-9
Number of pages	7
Journal	Bioorganic & Medicinal Chemistry
Volume	17
Issue number	13
DOIs	https://doi.org/10.1016/j.bmc.2009.05.002
Publication status	Published - 1 Jul 2009

Keywords

Amino Acid Sequence
Antifungal Agents
Bacterial Proteins
Candida albicans
Carbonic Anhydrase Inhibitors
Carbonic Anhydrases
Cryptococcus neoformans
Helicobacter pylori
Humans
Models, Molecular
Molecular Sequence Data
Protein Binding
Protein Conformation
Sequence Alignment
Structure-Activity Relationship
Sulfonamides

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10.1016/j.bmc.2009.05.002

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title = "Carbonic anhydrase inhibitors. Inhibition and homology modeling studies of the fungal beta-carbonic anhydrase from Candida albicans with sulfonamides",

abstract = "The beta-carbonic anhydrase (CA, EC 4.2.1.1) from the fungal pathogen Candida albicans (Nce103) is involved in a CO(2) sensing pathway critical for the pathogen life cycle and amenable to drug design studies. Herein we report an inhibition study of Nce103 with a library of sulfonamides and one sulfamate, showing that Nce103, similarly to the related enzyme from Cryptococcus neoformans Can2, is inhibited by these compounds with K(I)s in the range of 132 nM-7.6 microM. The best Nce103 inhibitors were acetazolamide, methazolamide, bromosulfanilamide, and 4-hydroxymethylbenzenesulfonamide (K(I)s",

keywords = "Amino Acid Sequence, Antifungal Agents, Bacterial Proteins, Candida albicans, Carbonic Anhydrase Inhibitors, Carbonic Anhydrases, Cryptococcus neoformans, Helicobacter pylori, Humans, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Conformation, Sequence Alignment, Structure-Activity Relationship, Sulfonamides",

author = "Alessio Innocenti and Rebecca Hall and Christine Schlicker and Andrea Scozzafava and Clemens Steegborn and M{\"u}hlschlegel, {Fritz A} and Supuran, {Claudiu T}",

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doi = "10.1016/j.bmc.2009.05.002",

language = "English",

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T1 - Carbonic anhydrase inhibitors. Inhibition and homology modeling studies of the fungal beta-carbonic anhydrase from Candida albicans with sulfonamides

AU - Innocenti, Alessio

AU - Hall, Rebecca

AU - Schlicker, Christine

AU - Scozzafava, Andrea

AU - Steegborn, Clemens

AU - Mühlschlegel, Fritz A

AU - Supuran, Claudiu T

PY - 2009/7/1

Y1 - 2009/7/1

N2 - The beta-carbonic anhydrase (CA, EC 4.2.1.1) from the fungal pathogen Candida albicans (Nce103) is involved in a CO(2) sensing pathway critical for the pathogen life cycle and amenable to drug design studies. Herein we report an inhibition study of Nce103 with a library of sulfonamides and one sulfamate, showing that Nce103, similarly to the related enzyme from Cryptococcus neoformans Can2, is inhibited by these compounds with K(I)s in the range of 132 nM-7.6 microM. The best Nce103 inhibitors were acetazolamide, methazolamide, bromosulfanilamide, and 4-hydroxymethylbenzenesulfonamide (K(I)s

AB - The beta-carbonic anhydrase (CA, EC 4.2.1.1) from the fungal pathogen Candida albicans (Nce103) is involved in a CO(2) sensing pathway critical for the pathogen life cycle and amenable to drug design studies. Herein we report an inhibition study of Nce103 with a library of sulfonamides and one sulfamate, showing that Nce103, similarly to the related enzyme from Cryptococcus neoformans Can2, is inhibited by these compounds with K(I)s in the range of 132 nM-7.6 microM. The best Nce103 inhibitors were acetazolamide, methazolamide, bromosulfanilamide, and 4-hydroxymethylbenzenesulfonamide (K(I)s

KW - Amino Acid Sequence

KW - Antifungal Agents

KW - Bacterial Proteins

KW - Candida albicans

KW - Carbonic Anhydrase Inhibitors

KW - Carbonic Anhydrases

KW - Cryptococcus neoformans

KW - Helicobacter pylori

KW - Humans

KW - Models, Molecular

KW - Molecular Sequence Data

KW - Protein Binding

KW - Protein Conformation

KW - Sequence Alignment

KW - Structure-Activity Relationship

KW - Sulfonamides

U2 - 10.1016/j.bmc.2009.05.002

DO - 10.1016/j.bmc.2009.05.002

M3 - Article

C2 - 19450983

SN - 0968-0896

VL - 17

SP - 4503

EP - 4509

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

IS - 13

ER -

Carbonic anhydrase inhibitors. Inhibition and homology modeling studies of the fungal beta-carbonic anhydrase from Candida albicans with sulfonamides

Abstract

Keywords

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