A thiabendazole sulfonamide shows potent inhibitory activity against mammalian and nematode alpha-carbonic anhydrases

Letizia Crocetti; Alfonso Maresca; Claudia Temperini; Rebecca Hall; Andrea Scozzafava; Fritz A Mühlschlegel; Claudiu T Supuran

doi:10.1016/j.bmcl.2009.01.038

A thiabendazole sulfonamide shows potent inhibitory activity against mammalian and nematode alpha-carbonic anhydrases

Letizia Crocetti
, Alfonso Maresca
, Claudia Temperini
, Rebecca Hall
, Andrea Scozzafava
, Fritz A Mühlschlegel
, Claudiu T Supuran

Biosciences

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

21 Citations (Scopus)

Abstract

A sulfonamide derivative of the antihelmintic drug thiabendazole was prepared and investigated for inhibition of the zinc enzyme carbonic anhydrase CA (EC 4.2.1.1). Mammalian isoforms CA I-XIV and the nematode enzyme of Caenorhabditis elegans CAH-4b were included in this study. Thiabendazole-5-sulfonamide was a very effective inhibitor of CAH-4b and CA IX (K(I)s of 6.4-9.5nm) and also inhibited effectively isozymes CA I, II, IV-VII, and XII, with K(I)s in the range of 17.8-73.2nM. The high resolution X-ray crystal structure of its adduct with isozyme II evidenced the structural elements responsible for this potent inhibitory activity.

Original language	English
Pages (from-to)	1371-5
Number of pages	5
Journal	Bioorganic & Medicinal Chemistry Letters
Volume	19
Issue number	5
DOIs	https://doi.org/10.1016/j.bmcl.2009.01.038
Publication status	Published - 1 Mar 2009

Keywords

Animals
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Carbonic Anhydrase Inhibitors
Carbonic Anhydrases
Crystallography, X-Ray
Mammals
Sulfonamides
Thiabendazole

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10.1016/j.bmcl.2009.01.038

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title = "A thiabendazole sulfonamide shows potent inhibitory activity against mammalian and nematode alpha-carbonic anhydrases",

abstract = "A sulfonamide derivative of the antihelmintic drug thiabendazole was prepared and investigated for inhibition of the zinc enzyme carbonic anhydrase CA (EC 4.2.1.1). Mammalian isoforms CA I-XIV and the nematode enzyme of Caenorhabditis elegans CAH-4b were included in this study. Thiabendazole-5-sulfonamide was a very effective inhibitor of CAH-4b and CA IX (K(I)s of 6.4-9.5nm) and also inhibited effectively isozymes CA I, II, IV-VII, and XII, with K(I)s in the range of 17.8-73.2nM. The high resolution X-ray crystal structure of its adduct with isozyme II evidenced the structural elements responsible for this potent inhibitory activity.",

keywords = "Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Carbonic Anhydrase Inhibitors, Carbonic Anhydrases, Crystallography, X-Ray, Mammals, Sulfonamides, Thiabendazole",

author = "Letizia Crocetti and Alfonso Maresca and Claudia Temperini and Rebecca Hall and Andrea Scozzafava and M{\"u}hlschlegel, \{Fritz A\} and Supuran, \{Claudiu T\}",

year = "2009",

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doi = "10.1016/j.bmcl.2009.01.038",

language = "English",

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journal = "Bioorganic \& Medicinal Chemistry Letters",

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T1 - A thiabendazole sulfonamide shows potent inhibitory activity against mammalian and nematode alpha-carbonic anhydrases

AU - Crocetti, Letizia

AU - Maresca, Alfonso

AU - Temperini, Claudia

AU - Hall, Rebecca

AU - Scozzafava, Andrea

AU - Mühlschlegel, Fritz A

AU - Supuran, Claudiu T

PY - 2009/3/1

Y1 - 2009/3/1

N2 - A sulfonamide derivative of the antihelmintic drug thiabendazole was prepared and investigated for inhibition of the zinc enzyme carbonic anhydrase CA (EC 4.2.1.1). Mammalian isoforms CA I-XIV and the nematode enzyme of Caenorhabditis elegans CAH-4b were included in this study. Thiabendazole-5-sulfonamide was a very effective inhibitor of CAH-4b and CA IX (K(I)s of 6.4-9.5nm) and also inhibited effectively isozymes CA I, II, IV-VII, and XII, with K(I)s in the range of 17.8-73.2nM. The high resolution X-ray crystal structure of its adduct with isozyme II evidenced the structural elements responsible for this potent inhibitory activity.

AB - A sulfonamide derivative of the antihelmintic drug thiabendazole was prepared and investigated for inhibition of the zinc enzyme carbonic anhydrase CA (EC 4.2.1.1). Mammalian isoforms CA I-XIV and the nematode enzyme of Caenorhabditis elegans CAH-4b were included in this study. Thiabendazole-5-sulfonamide was a very effective inhibitor of CAH-4b and CA IX (K(I)s of 6.4-9.5nm) and also inhibited effectively isozymes CA I, II, IV-VII, and XII, with K(I)s in the range of 17.8-73.2nM. The high resolution X-ray crystal structure of its adduct with isozyme II evidenced the structural elements responsible for this potent inhibitory activity.

KW - Animals

KW - Caenorhabditis elegans

KW - Caenorhabditis elegans Proteins

KW - Carbonic Anhydrase Inhibitors

KW - Carbonic Anhydrases

KW - Crystallography, X-Ray

KW - Mammals

KW - Sulfonamides

KW - Thiabendazole

U2 - 10.1016/j.bmcl.2009.01.038

DO - 10.1016/j.bmcl.2009.01.038

M3 - Article

C2 - 19186056

SN - 0960-894X

VL - 19

SP - 1371

EP - 1375

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

IS - 5

ER -

A thiabendazole sulfonamide shows potent inhibitory activity against mammalian and nematode alpha-carbonic anhydrases

Abstract

Keywords

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