Discovery of novel 1,3-diaryltriazene sulfonamides as carbonic anhydrase I, II, VII, and IX inhibitors

A series of new 1,3-diaryltriazene sulfonamides was synthesised by reaction of diazonium salt of metanilamide (3-aminobenzene sulfonamide) with substituted aromatic amines. The obtained new compounds were assayed as inhibitors of four physiologically and pharmacologically relevant human (h) isoforms of carbonic anhydrases (CA, EC 4.2.1.1), specifically, hCA I, hCA II, and hCA VII (cytosolic isoforms), as well as the tumour-associated membrane-bound isoform hCA IX. All isoforms investigated here were inhibited by the newly synthesised 1,3-diaryltriazene sulfonamide derivatives from the micromolar to the nanomolar range. The cytosolic isoforms were inhibited with Kis in the range of 92.3–8371.1 nM (hCA I), 4.3–9194.0 nM (hCA II), and 15.6–9477.8 nM (hCA VII), respectively. For the membrane-bound tumour-associated isoform hCA IX, the KI-s ranged between 50.8 and 9268.5 nM. The structure–activity relationship (SAR) with these newly synthesised metanilamide derivatives are discussed in detail

Synthesis and biological evaluation of histamine Schiff bases as carbonic anhydrase I, II, IV, VII, and IX activators

A series of 20 histamine Schiff base was synthesised by reaction of histamine, a well known carbonic anhydrase (CA, E.C 4.2.2.1.) activator pharmacophore, with substituted aldehydes. The obtained histamine Schiff bases were assayed as activators of five selected human (h) CA isozymes, the cytosolic hCA I, hCA II, and hCA VII, the membrane-anchored hCA IV and transmembrane hCA IX. Some of these compounds showed efficient activity (in the nanomolar range) against the cytosolic isoform hCA VII, which is a key CA enzyme involved in brain metabolism. Moderate activity was observed against hCA I and hCA IV (in the nanomolar to low micromolar range). The structure–activity relationship for activation of these isoforms with the new histamine Schiff bases is discussed in detail based on the nature of the aliphatic, aromatic, or heterocyclic moiety present in the aldehyde fragment of the molecule, which may participate in diverse interactions with amino acid residues at the entrance of the active site, where activators bind, and which is the most variable part among the different CA isoforms

Poly(N-vinyl-2-pyrrolidone) Stabilized Nanoclusters as Highly Efficient and Reusable Catalyst for the Dehydrogenation of Dimethly Ammonia-Borane

Addressed herein, we report a highly efficient and facile synthesis of palladium, nickel nanoparticles supported on poly(N-vinyl-2-pyrrolidone) (PdNi@PVP NPs) for the dehydrogenation of DMAB. PdNi@PVP nanoclusters have been synthesized from the reduction of precursors of metals (Pd and Ni) by the microwave assistance method at room temperature with an average particle size of 3.05 +/- 0.38 nm. This newly produced monodisperse PdNi@PVP nanoclusters exhibits high durability, reusability, and catalytic performance even after the fourth cycle of dehydrogenation of DMAB reactions. On the other hand, the structure morphology and properties of the nanoclusters were characterized using different analytical methods such as UV-Vis, XPS, XRD, TEM, and the HR-TEM techniques. Besides, the PdNi@PVP NPs catalyst showed good catalytic effectiveness with a high turnover frequency of 561.0 h(-1) and low Ea value of 37.11 +/- 2 kJ mol(-1) for DMAB dehydrocoupling in ambient conditions

Synthesis and cytotoxic activities of novel copper and silver complexes of 1,3-diaryltriazene-substituted sulfonamides

In this study, a series of 10 novel copper (II) and silver complexes of 1,3-diaryltriazene-substituted sulfonamides was synthesised. All the synthesised ligands and their metal complexes were assessed for in vitro cytotoxicity against human colorectal adenocarcinoma (DLD-1), cervix carcinoma (HeLa), breast adenocarcinoma (MDA-MB-231), colon adenocarcinoma (HT-29), endometrial adenocarcinoma (ECC-1), prostate cancer (DU-145 and PC-3), normal embryonic kidney (HEK-293), normal prostate epithelium (PNT-1A), and normal retinal pigment epithelium (ARPE-19) cells. Most of the metal complexes from the series showed to be more active against all cancerous cells than the uncomplexed 1,3-diaryltriazene-substituted sulfonamides, and lower cytotoxic effects observed on normal cells. Most of the Cu (II) and Ag (I) metal complexes from the presented series showed high cytotoxic activity against HeLa cells with IC50 values ranging from 2.08 to >300 µM. Specifically, compound L3-Ag showed one of the highest cytotoxicity against all cancer cell lines with IC50 values between 3.30 to 16.18 µM among other tested compounds

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

Design, synthesis and biological evaluation of 1,3-diaryltriazene-substituted sulfonamides as antioxidant, acetylcholinesterase and butyrylcholinesterase inhibitors

1,3-diaryltriazenes are one of the most useful and important linkers for many pharmaceutical applications. Therefore, in the current work, a series of 1,3-diaryltriazene sulfonamides 4(a-k) were synthesized by reacting diazonium salt of sulfanilamide and substituted aromatic amine derivatives 3(a-k). The obtained compounds were investigated for antioxidant properties by using different methods such as a DPPH radical scavenging assay, ABTS radical decolarization, cupric reducing antioxidant capacity (CUPRAC) and metal chelating methods. The cholinesterase inhibition activities (acetylcholinesterase and butyrylcholinesterase) of synthesized compounds were also tested. In general, compounds showed weak antioxidant activity, except compounds 4d (IC50 =114.89 for DPPH activity), 4i (IC50 =25.31 for ABTS activity), 4a (IC50 = 86.33 for metal chelating activity), and 4k (absorbance value 1.229 µM for CUPRAC). Some of the compounds showed great % inhibition against both acetylcholinesterase and butyrylcholinesterase with % inhibition values ranging from 11.54 to 93.67 and 62.24 to 98.47, respectively

Potent carbonic anhydrase I, II, IX and XII inhibition activity of novel primary benzenesulfonamides incorporating bis-ureido moieties

AbstractA novel series of twelve aromatic bis-ureido-substituted benzenesulfonamides was synthesised by conjugation of aromatic aminobenzenesulfonamides with aromatic bis-isocyanates. The obtained bis-ureido-substituted derivatives were tested against four selected human carbonic anhydrase isoforms (hCA I, hCA II, hCA IX and hCA XII). Most of the new compounds showed an effective inhibitory profile against isoforms hCA IX and hCA XII, also having some selectivity with respect to hCA I and hCA II. The inhibition constants of these compounds against isoforms hCA IX and XII were in the range of 6.73–835 and 5.02–429 nM, respectively. Since hCA IX and hCA XII are important drug targets for anti-cancer/anti-metastatic drugs, these effective inhibitors reported here may be considered of interest for cancer related studies in which these enzymes are involved