A series of 1,3,5-triazinyl aminobenzenesulfonamides substituted by aminoalcohol, aminostilbene, and aminochalcone structural motifs was synthesized as potential human carbonic anhydrase (hCA) inhibitors. The compounds were evaluated on their inhibition of tumor-associated hCA IX and hCA XII, hCA VII isoenzyme present in the brain, and physiologically important hCA I and hCA II. While the test compounds had only a negligible effect on physiologically important isoenzymes, many of the studied compounds significantly affected the hCA IX isoenzyme. Several compounds showed activity against hCA XII; (E)-4-{2-[(4-[(2,3-dihydroxypropyl)amino]-6-[(4-styrylphenyl)amino]-1,3,5-triazin-2-yl)amino]ethyl}benzenesulfonamide (31) and (E)-4-{2-[(4-[(4-hydroxyphenyl)amino]-6-[(4-styrylphenyl)amino]-1,3,5-triazin-2-yl)amino]ethyl}benzenesulfonamide (32) were the most effective inhibitors with KIs = 4.4 and 5.9 nM, respectively. In addition, the compounds were tested against vancomycin-resistant Enterococcus faecalis (VRE) isolates. (E)-4-[2-({4-[(4-cinnamoylphenyl)amino]-6-[(4-hydroxyphenyl)amino]-1,3,5-triazin-2-yl}amino)ethyl]benzenesulfonamide (21) (MIC = 26.33 µM) and derivative 32 (MIC range 13.80-55.20 µM) demonstrated the highest activity against all tested strains. The most active compounds were evaluated for their cytotoxicity against the Human Colorectal Tumor Cell Line (HCT116 p53 +/+). Only 4,4'-[(6-chloro-1,3,5-triazin-2,4-diyl)bis(iminomethylene)]dibenzenesulfonamide (7) and compound 32 demonstrated an IC50 of ca. 6.5 μM; otherwise, the other selected derivatives did not show toxicity at concentrations up to 50 µM. The molecular modeling and docking of active compounds into various hCA isoenzymes, including bacterial carbonic anhydrase, specifically α-CA present in VRE, was performed to try to outline a possible mechanism of selective anti-VRE activity.

• Keywords
• benzenesulfonamide, carbonic anhydrase, chalcone, inhibition, stilbene, triazine, vancomycin-resistant enterococci,
• MeSH
• Anti-Bacterial Agents pharmacology   MeSH
• Vancomycin-Resistant Enterococci drug effects   MeSH
• HCT116 Cells MeSH
• Carbonic Anhydrase Inhibitors pharmacology   MeSH
• Carbonic Anhydrase I antagonists & inhibitors   MeSH
• Carbonic Anhydrase II antagonists & inhibitors   MeSH
• Carbonic Anhydrase IX antagonists & inhibitors   MeSH
• Carbonic Anhydrases drug effects   MeSH
• Humans MeSH
• Neoplasms drug therapy   MeSH
• Antineoplastic Agents pharmacology   therapeutic use   MeSH
• Molecular Dynamics Simulation MeSH
• Molecular Docking Simulation MeSH
• Sulfonamides pharmacology   MeSH
• Structure-Activity Relationship MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Bacterial Agents MeSH
• carbonic anhydrase XII MeSH Browser
• Carbonic Anhydrase Inhibitors MeSH
• Carbonic Anhydrase I MeSH
• Carbonic Anhydrase II MeSH
• Carbonic Anhydrase IX MeSH
• Carbonic Anhydrases MeSH
• Antineoplastic Agents MeSH
• Sulfonamides MeSH

A series of 1,3,5-triazine analogues, incorporating aminobenzene sulfonamide, aminoalcohol/phenol, piperazine, chalcone, or stilbene structural motifs, were evaluated as potential antioxidants. The compounds were prepared by using step-by-step nucleophilic substitution of chlorine atoms in starting 2,4,6-trichloro-1,3,5-triazine. Reactions were catalyzed by Cu(I)-supported on a weakly acidic resin. The radical scavenging activity was determined in terms of %inhibition activity and EC50, using the ABTS method. Trolox and ascorbic acid (ASA) were used as standards. In the lowest concentration 1 × 10-4 M, the %inhibition activity values at 0 min were comparable with both standards at least for 10 compounds. After 60 min, compounds 5, 6, 13, and 25 showed nearly twice %inhibition (73.44-87.09%) in comparison with the standards (Trolox = 41.49%; ASA = 31.07%). Values of EC50 at 60 min (17.16-27.78 μM) were 5 times lower for compounds 5, 6, 13, and 25 than EC50 of both standards (trolox = 178.33 μM; ASA = 147.47 μM). Values of EC50 correlated with %inhibition activity. Based on these results, the presented 1,3,5-triazine analogues have a high potential in the treatment of illnesses caused or related to oxidative stress.

• Keywords
• 1,3,5-triazine, 4-aminophenol, ABTS method, antioxidative activity, hydroxychalcone, hydroxystilbene,
• MeSH
• Antioxidants chemical synthesis   chemistry   pharmacology   MeSH
• Chalcone chemistry   MeSH
• Phenol chemistry   MeSH
• Molecular Structure MeSH
• Piperazine chemistry   MeSH
• Sulfonamides chemistry   MeSH
• Chemistry Techniques, Synthetic MeSH
• Triazines chemical synthesis   chemistry   pharmacology   MeSH
• Structure-Activity Relationship MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Antioxidants MeSH
• Chalcone MeSH
• Phenol MeSH
• Piperazine MeSH
• Sulfonamides MeSH
• Triazines MeSH

An efficient and simple methodology for Ullmann Cu(I)-catalyzed synthesis of di- and trisubstituted 1,3,5-triazine derivatives from dichlorotriazinyl benzenesulfonamide and corresponding nucleophiles is reported. Cations Cu(I) supported on macroporous and weakly acidic, low-cost industrial resin of polyacrylate type were used as a catalyst. The reaction times and yields were compared with traditional synthetic methods for synthesis of substituted 1,3,5-triazine derivatives via nucleophilic substitution of chlorine atoms in dichlorotriazinyl benzenesulfonamide. It was found that Ullmann-type reactions provide significantly shortened reaction times and, in some cases, also higher yields. Finally, trisubstituted s-triazine derivatives were effectively prepared via Ullmann-type reaction in a one-pot synthetic design. Six new s-triazine derivatives with potential biological activity were prepared and characterized.

• Keywords
• 1,3,5-triazine, Ullmann reaction, one-pot synthesis, supported Cu(I) catalyst,
• MeSH
• Catalysis MeSH
• Copper chemistry   MeSH
• Molecular Structure MeSH
• Porosity MeSH
• Triazines chemical synthesis   chemistry   MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH
• Names of Substances
• Copper MeSH
• Triazines MeSH