Carbonic anhydrase inhibitors: synthesis and inhibition studies against mammalian isoforms I-XV with a series of 2-(hydrazinocarbonyl)-3-substituted-phenyl-1H-indole-5-sulfonamides.

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Guzel O, Innocenti A, Scozzafava A, Salman A, Parkkila S, Hilvo M, Supuran CT

Carbonic anhydrase inhibitors: synthesis and inhibition studies against mammalian isoforms I-XV with a series of 2-(hydrazinocarbonyl)-3-substituted-phenyl-1H-indole-5-sulfonamides.

Bioorg Med Chem. 2008 Oct 15;16(20):9113-20. doi: 10.1016/j.bmc.2008.09.032. Epub 2008 Sep 13.

PubMed ID

18819811 [ View in PubMed

]

Abstract

A series of 2-(hydrazinocarbonyl)-3-substitutedphenyl-1H-indole-5-sulfonamides possessing various 2-, 3- or 4- substituted phenyl groups with methyl-, halogeno- and methoxy- functionalities, as well as the perfluorophenyl moiety have been synthesized and evaluated as inhibitors of 13 catalytically active, mammalian carbonic anhydrase (CA, EC 4.2.1.1) isoforms, that is, CA I-CA XV (of human (h) or murine (m) origin). The new compounds were ineffective inhibitors of isozymes hCA III, hCA IV, hCA VA, hCA VB, hCA VI and mCA XIII, moderate inhibitors of hCA I, hCA VII, hCA IX and mCA XV, and excellent, low-nanomolar inhibitors of hCA II and hCA XIV. The substitution pattern of the aromatic group in the 3-position of the indole ring influenced biological activity and isozyme inhibition profiles in this series of sulfonamides. Some of the best and most selective hCA XIV and mCA XV inhibitors ever reported have been identified in this study.

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Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
2-(hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide	Carbonic anhydrase 2	Ki (nM)	7.2	7.4	25	Details