Sulphonamides incorporating 1,3,5-triazine structural motifs show antioxidant, acetylcholinesterase, butyrylcholinesterase, and tyrosinase inhibitory profile.

A series of 16 novel benzenesulfonamides incorporating 1,3,5-triazine moieties substituted with aromatic amines, dimethylamine, morpholine and piperidine were investigated. These compounds were assayed for antioxidant properties by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay, 2,2`-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical decolarisation assay and metal chelating methods. They were also investigated as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and tyrosinase, which are associated with several diseases such as Alzheimer, Parkinson and pigmentation disorders. These benzenesulfonamides showed moderate DPPH radical scavenging and metal chelating activity, and low ABTS cation radical scavenging activity. Compounds 2 b, 3d and 3 h showed inhibitory potency against AChE with % inhibition values of >90. BChE was also effectively inhibited by most of the synthesised compounds with >90% inhibition potency. Tyrosinase was less inhibited by these compounds.

α-Carbonic anhydrases are strongly activated by spinaceamine derivatives.

A series of 4-substituted-spinaceamine (4,5,6,7-tetrahydro-imidazolo[4,5-c]pyridine) were prepared from histamine and aromatic aldehydes Schiff bases, and investigated as activators of four human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the cytosolic hCA I, II and VII, and the membrane-associated hCA IV. All isoforms were effectively activated by the new derivatives, and the nature of the moiety in position 4 of the bicyclic system was the factor influencing activation properties against all isoforms. For hCA I, these compounds showed KAs in the range of 2.52-21.5 µM, the most effective activator being 4-(2-hydroxyphenyl)-spinaceamine. For hCA II the activation constants ranged between 0.60 and 17.2 µM, with 4-(2,3,5,6-tetrafluorophenyl)- spinaceamine the best activator. Affinity for hCA IV was in the range of 0.52-63.8 µM, and the same compound as for hCA II was the most effective activator. The most sensitive isoform for activation was the brain-associated hCA VII, for which KAs in the range of 82 nM-4.26 µM were observed. Effective hCA VII activators were the (2-bromophenyl)-, 2,3,5,6-tetrafluorophenyl- and furyl-substituted spineaceamines (KAs of 82-95 nM). As CA activators may have pharmacologic applications in various fields, this work provides interesting derivatives for further studies.

Synthesis and biological evaluation of novel aromatic and heterocyclic bis-sulfonamide Schiff bases as carbonic anhydrase I, II, VII and IX inhibitors.

A series of sixteen novel aromatic and heterocyclic bis-sulfonamide Schiff bases were prepared by conjugation of well known aromatic and heterocyclic aminosulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitor pharmacophores with aromatic and heterocyclic bis-aldehydes. The obtained bis-sulfonamide Schiff bases were investigated as inhibitors of four selected human (h) CA isoforms, hCA I, hCA II, hCA VII and hCA IX. Most of the newly synthesized compounds showed a good inhibitory profile against isoforms hCA II and hCA IX, also showing moderate selectivity against hCA I and VII. Several efficient lead compounds were identified among this bis-sulfonamide Schiff bases with low nanomolar to sub-nanomolar activity against hCA II (Kis ranging between 0.4 and 861.1nM) and IX (Kis between 0.5 and 933.6nM). Since hCA II and hCA IX are important drug targets (antiglaucoma and anti-tumor agents), these isoform-selective inhibitors may be considered of interest for various biomedical applications.