RESUMO
Starting from 4-amino-antipyrine, six new compounds were synthesized and characterized. The new compounds contain moieties with particular properties, such are ionophore (benzo-15-crown-5), fluorescent (nitrobenzofurazan), stable free radical (nitroxide), or other types of biological active residues, like nitroderivatives, antipyrine or isoniazid residues. They were fully characterized by appropriate means ((1)H and (13)C NMR, IR, UV-Vis, fluorescence, EPR, elemental analysis) and some of their biological properties were evaluated. Hydrophobicity (R(M0), log P), total antioxidant capacity (TAC), and antimicrobial properties are also presented and discussed.
Assuntos
Antibacterianos/síntese química , Antioxidantes/síntese química , Antipirina/análogos & derivados , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Pirazolonas/síntese química , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Antipirina/síntese química , Antipirina/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Positivas/crescimento & desenvolvimento , Humanos , Interações Hidrofóbicas e Hidrofílicas , Espectroscopia de Ressonância Magnética , Pirazolonas/farmacologia , Espectrometria de Fluorescência , Relação Estrutura-AtividadeRESUMO
The 3+2 cycloaddition reaction of 1-(4-phenylphenacyl)-1,10-phenanthrolinium ylide 4 with activated alkynes gave pyrrolo[1,2- 4a][1,10]phenanthrolines 6a-d. The "one pot" synthesis of 6a,b,d from 4, activated alkenes, Et(3)N and tetrakis-pyridine cobalt (II) dichromate (TPCD) is described. The helical chirality of pyrrolophenanthrolines 6b-d was put in evidence by NMR spectroscopy.
Assuntos
Alcinos/química , Cicloparafinas/química , Compostos Heterocíclicos/síntese química , Catálise , Ciclização , Modelos Biológicos , Fenantrolinas/química , EstereoisomerismoRESUMO
Important physiological and physio-pathological functions are played by several carbonic anhydrase (CA, EC 4.2.1.1) isozymes, which are strongly inhibited by aromatic and heterocyclic sulfonamides. Here we report several new types of such sulfonamides, incorporating furan-, thiophene- and pyrrole-carboxamide moieties in their molecules. Some of these compounds showed very good CA II and CA IV inhibitory properties. with affinities for the enzymes in the low nanomolar range. Due to their relatively low water solubility, some of the most active CA II inhibitors reported here have been formulated as aqueous suspension for topical administration as antiglaucoma agents. in normotensive and glaucomatous rabbits. The derivatives incorporating furan- and pyrrole-carboxamide moieties (but not the corresponding thiophene-substituted derivatives), showed effective and long-lasting intraocular pressure (IOP) lowering both in normotensive as well as glaucomatous animals, with potencies superior to dorzolamide and brinzolamide, the two available topically acting sulfonamide drugs. This is the first example of non-water soluble sulfonamides that significantly lower IOP, being thus similar with the recently introduced drug brinzolamide, which belongs to a completely different chemical family of antiglaucoma sulfonamides.
