A series of novel sulphonamide derivatives was obtained from sulphanilamide which was N4-alkylated with ethyl bromoacetate followed by reaction with hydrazine hydrate. The hydrazide obtained was further reacted with various aromatic aldehydes. The novel sulphonamides were characterised by infrared, mass spectrometry, 1H- and 13C-NMR and purity was determined by high-performance liquid chromatography (HPLC). Human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA I and II and Mycobacterium tuberculosis β-CA encoded by the gene Rv3273 (mtCA 3) inhibition activity was investigated with the synthesised compounds which showed promising inhibition. The KIs were in the range of 54.6 nM–1.8 µM against hCA I, in the range of 32.1 nM–5.5 µM against hCA II and of 127 nM–2.12 µM against mtCA 3.

A series of new Schiff's bases was obtained from the sulfanilamide semicarbazone (4-aminosulfonylphenyl semicarbazide) and aromatic/heterocyclic aldehydes. The new compounds were designed to incorporate moieties known to induce effective inhibitory activity against carbonic anhydrase (CA, EC 4.2.1.1) isoforms involved in crucial physiologic or pathologic processes such as the cytosolic CA I and II or the transmembrane, tumor-associated CA IX and XII: the compounds were medium potency -weak CA I inhibitors, highly effective, low nanomolar CA II inhibitors, but few of them inhibited effectively CA IX and XII. This may probably due to the long spacer between the sulfamoylphenyl and imine fragments of the molecules, which probably induces a highly flexible conformation of the inhibitor bound to the active site of the enzyme, with destabilizing effects for the adduct. The detailed structure activity relationship for this class of inhibitors is discussed.

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 parasubstitution 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.

Myristoyl-CoA:Protein N-myristoyltranferase (NMT) is a cytosolic monomeric enzyme which catalyses the transfer of a rare fatty acid, myristate from myristoyl-CoA to the N-terminal glycine residue of a variety of eukaryotic and viral proteins. N-myristoyltransferase is a novel target for anticancer, antiviral and antifungal agents. Recent N-myristoyltransferase inhibitors like benzofurans and benzothiazole derivatives show in vivo antifungal activity and are promising selective fungal N-myristoyltransferase inhibitors.

Aim: Human carbonic anhydrase (CA, EC 4.2.1.1) isoforms IX and XII are validated antitumor/antimetastatic drug and tumor imaging targets with sulfonamide inhibitors and monoclonal antibodies in clinical development. Coumarins act as isoform-selective inhibitors of these isoforms over the cytosolic and mitochondrial ones. background: Human carbonic anhydrase (CA, EC 4.2.1.1) isoforms IX and XII are validated antitumor/antimetastatic drug and tumor imaging targets, with sulfonamide inhibitors and monoclonal antibodies in clinical development. Materials and Methods: We report the synthesis and in vitro CA inhibitory evaluation of a large panel of coumarins incorporating pyrazole-1-carboxamide moieties. Compounds were fully characterized before the assessment of their inhibitory activity. A stopped-flow CO2 hydrase assay was performed for the biological test. objective: Coumarins act as isoform-selective inhibitors of these isoforms over the cytosolic and mitochondrial ones. Results: These coumarins did not inhibit the widespread, off-target isoforms CA I and II (KI 50 μM), but they were sub-micromolar CA IX/XII inhibitors with an interesting selectivity index higher than the reference compound. Selectivity between α- and β-class of CAs was also promising. method: We report the synthesis and in vitro CA inhibitory evaluation of a large panel of coumarins incorporating pyrazole-1-carboxamide moieties. Compounds were fully characterized before the assessment of their inhibitory activity. The biological test was performed by a stopped-flow CO2 hydrase assay. Conclusion: These compounds may be used as leads for the rational design and development of non-sulfonamide CA IX/XII effective inhibitors. conclusion: These compounds may be used as leads for the rational design and development of non-sulfonamide CA IX/XII effective inhibitors.