25165-72-4Relevant articles and documents
Chemical synthesis, molecular docking and MepA efflux pump inhibitory effect by 1,8-naphthyridines sulfonamides
Oliveira-Tintino, Cícera Datiane de Morais,Tintino, Saulo Relison,Muniz, Débora Feitosa,Rodrigues dos Santos Barbosa, Cristina,Pereira, Raimundo Luiz Silva,Begnini, Iêda Maria,Rebelo, Ricardo Andrade,da Silva, Luiz Everson,Mireski, Sandro Lucio,Nasato, Michele Caroline,Krautler, Maria Isabel Lacowicz,Pereira, Pedro Silvino,Balbino, Tereza Cristina Leal,da Costa, José Galberto Martins,Rodrigues, Fabiola Fernandes Galv?o,Teixeira, Alexandre Magno Rodrigues,Barreto, Humberto Medeiros,de Menezes, Irwin Rose Alencar,Coutinho, Henrique Douglas Melo,da Silva, Teresinha Gon?alves
, (2021/02/26)
This study aimed to evaluate the antibacterial activity and to verify, in silico and in vitro, the inhibition of efflux mechanisms using a series of synthesized 1,8-naphthyridines sulfonamides against Staphylococcus aureus strains carrying MepA efflux pumps. The chemical synthesis occurred through the thermolysis of the Meldrum's acid adduct. The sulfonamide derivatives were obtained by the sulfonylation of 2-amino-5?chloro-1,8-naphthyridine with commercial benzenesulfonyl chloride. Antibacterial activity was assessed by the broth microdilution test. Efflux pump inhibitory capacity was evaluated in silico by molecular docking and in vitro by analyzing synergistic effects on ciprofloxacin and ethidium bromide (EtBr) and by EtBr fluorescence emission assays. The following 1,8-naphthyridines were synthesized: 4-methyl-N-(5?chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10a); 2,5-dichloro-N-(5?chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10b); 4-fluoro-N-(5?chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10c); 2,3,4-trifluoro-N-(5?chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10d); 3-trifluoromethyl-N-(5?chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10e); 4?bromo-2,5-difluoro-N-(5?chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide (Compound 10f). The 1,8-naphthyridines derivatives associated with sulfonamides did not show antibacterial activity. However, they showed a favorable pharmacokinetic profile with possible MepA efflux pump inhibitory action, demonstrated in molecular docking. In addition to the promising results in reducing the concentration of intracellular EtBr. 1,8-naphthyridines act as putative agents in the inhibitory action of the MepA efflux pump.
Quinoline derivatives inhibiting the effect of growth factors such as VEGF
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Page column 65, (2010/02/08)
Compounds of the formula (I): wherein: R2represents hydroxy, halogeno, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino or nitro; n is an integer from 0 to 5; Z represents —O—, —NH—, —S— or —CH2—; G1represents phenyl or a 5-10 membered heteroaromatic cyclic or bicyclic group; Y1, Y2, Y3and Y4each independently represents carbon or nitrogen; R1represents fluoro or hydrogen; m is an integer from 1 to 3; R3represents hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, C1-3alkyl, —NR4R5(wherein R4and R5, can each be hydrogen or C1-3alkyl), or a group R6—X1— wherein X1represents —CH2— or a heteroatom linker group and R6is an alkyl, alkenyl or alkynyl chain optionally substituted by for example hydroxy, amino, nitro, alkyl, cycloalkyl, alkoxyalkyl, or an optionally substituted group selected from pyridone, phenyl and a heterocyclic ring, which alkyl, alkenyl or alkynyl chain may have a heteroatom linker group, or R6is an optionally substituted group selected from pyridone, phenyl and a heterocyclic ring and salts thereof, in the manufacture of a medicament for use in the production of an antiangiogenic and/or vascular permeability reducing effect in warm-blooded animals such as humans, processes for the preparation of such derivatives, pharmaceutical compositions containing a compound of formula I or a pharmaceutically acceptable salt thereof as active ingredient and compounds of formula I. The compounds of formula I and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.
