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Carbonic anhydrase inhibitors: design, synthesis, and biological evaluation of novel sulfonyl semicarbazide derivatives.

ABSTRACT: A series of novel sulfonyl semicarbazides 5-13 was designed, synthesized, and evaluated for human carbonic anhydrase (hCA) inhibition. The new sulfonyl semicarbazides were tested against a panel of hCA isoforms I, II, IX, and XII, using acetazolamide (AZA, 1) as standard. All the sulfonyl semicarbazides showed subnanomolar affinity for hCA XII (pK i range 0.59-0.79 nM) and high selectivity over hCA I (58-114-fold) and hCA IX (26-114-fold) compared to hCA II (5-20-fold except 11, 121-fold). The importance of the nature of para-substitution on the sulfonyl substituted aromatic ring for potency and selectivity against one hCA isoform versus others is discussed. Overall, the research work led to the development of highly potent and selective hCA inhibitors.

SUBMITTER: Pichake J

PROVIDER: S-EPMC4094246 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Carbonic anhydrase inhibitors: design, synthesis, and biological evaluation of novel sulfonyl semicarbazide derivatives.

Pichake Jayashree J Kharkar Prashant S PS Ceruso Mariangela M Supuran Claudiu T CT Toraskar Mrunmayee P MP

ACS medicinal chemistry letters 20140516 7

A series of novel sulfonyl semicarbazides 5-13 was designed, synthesized, and evaluated for human carbonic anhydrase (hCA) inhibition. The new sulfonyl semicarbazides were tested against a panel of hCA isoforms I, II, IX, and XII, using acetazolamide (AZA, 1) as standard. All the sulfonyl semicarbazides showed subnanomolar affinity for hCA XII (pK i range 0.59-0.79 nM) and high selectivity over hCA I (58-114-fold) and hCA IX (26-114-fold) compared to hCA II (5-20-fold except 11, 121-fold). The i ...[more]

PMID: 25050167

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