RESUMO
In the present investigation, a series of dihydrotriazine derivatives-bearing 5-aryloxypyrazole moieties were synthesized and their structures were confirmed by different spectral tools. The biological evaluation in vitro revealed that some of the target compounds exerted good antibacterial and antifungal activity in comparison with the reference drugs. Among these novel hybrids, compound 10d showed the most potent activity with minimum inhibitory concentration values (MIC) of 0.5 µg/mL against S. aureus 4220, MRSA 3506 and E. coli 1924 strain. The cytotoxic activity of the compounds 6d, 6m, 10d and 10g was assessed in MCF-7 and HeLa cells. Growth kinetics study showed significant inhibition of bacterial growth when treated with different conc. of 10d. In vitro enzyme study implied that compound 10d exerted its antibacterial activity through DHFR inhibition. Moreover, significant inhibition of biofilm formation was observed in bacterial cells treated with MIC conc. of 10d as visualized by SEM micrographs. Twenty-nine target compounds were designed, synthesized and evaluated in terms of their antibacterial and antifungal activities.
Assuntos
Antibacterianos , Triazinas , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Sobrevivência Celular/efeitos dos fármacos , Células HeLa , Humanos , Células MCF-7 , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Tetra-Hidrofolato Desidrogenase/química , Triazinas/síntese química , Triazinas/química , Triazinas/farmacologiaRESUMO
Twenty benzothiazole derivatives bearing a 1,3,4-oxadiazole moiety were synthesized and evaluated for their anti-oxidant and anti-inflammatory activities. Among these compounds, 8h and 8l were appeared to have high radical scavenging efficacies as 0.05 ± 0.02 and 0.07 ± 0.03 mmol/L of IC50 values in ABTS+ bioassay, respectively. In anti-inflammatory tests, compound 8h displayed good activity with 57.35% inhibition after intraperitoneal administration, which was more potent than the reference drug (indomethacin). Molecular modeling studies were performed to investigate the binding mode of the representative compound 8h into COX-2 enzyme. In vitro enzyme study implied that compound 8h exerted its anti-inflammatory activity through COX-2 inhibition.
Assuntos
Anti-Inflamatórios/uso terapêutico , Benzotiazóis/uso terapêutico , Sequestradores de Radicais Livres/uso terapêutico , Inflamação/tratamento farmacológico , Oxidiazóis/uso terapêutico , Animais , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/metabolismo , Benzotiazóis/síntese química , Benzotiazóis/metabolismo , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Sequestradores de Radicais Livres/síntese química , Sequestradores de Radicais Livres/metabolismo , Humanos , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Oxidiazóis/síntese química , Oxidiazóis/metabolismo , Relação Estrutura-AtividadeRESUMO
The present work describes the in vitro antibacterial evaluation of some new pyrimidine derivatives. Twenty-two target compounds were designed, synthesized and preliminarily explored for their antimicrobial activities. The antimicrobial assay revealed that some target compounds exhibited significantly inhibitory efficiencies toward bacteria and fungal including drug-resistant pathogens. Compound 7c presented the most potent inhibitory activities against Gram-positive bacteria (e.g., Staphylococcus aureus 4220), Gram-negative bacteria (e.g., Escherichia coli 1924) and the fungus Candida albicans 7535, with an MIC of 2.4 µmol/L. Compound 7c was also the most potent, with MICs of 2.4 or 4.8 µmol/L against four multidrug-resistant, Gram-positive bacterial strains. The toxicity evaluation of the compounds 7c, 10a, 19d and 26b was assessed in human normal liver cells (L02 cells). Molecular docking simulation and analysis suggested that compound 7c has a good interaction with the active cavities of dihydrofolate reductase (DHFR). In vitro enzyme study implied that compound 7c also displayed DHFR inhibition.