RESUMO
In this study, novel 4-(5-((2/3/4-substituted benzyl)thio)-4-(4-substituted phenyl)-4H-1,2,4-triazol-3-yl)-2-(pyridin-3/4-yl)thiazoles were synthesized following a multi-step synthetic procedure. All the compounds were screened with a panel of gram positive/negative bacteria, yeasts, and molds for antimicrobial activity using the disc diffusion method. Then, the minimum inhibitor concentration (MIC) and the minimum bactericidal concentration (MBC) values of active compounds were determined against Micrococcus luteus, Bacillus cereus, Listeria monocytogenes, and Staphylococcus aureus using the broth microdilution technique. These compounds were also screened for their inhibitory activities against S. aureus DNA gyrase by supercoiling assay. Furthermore, the crystal structure of S. aureus DNA gyrase B ATPase was subjected to a docking experiment to identify the possible interactions between the most active ligand and the active site. Lastly, the in silico technique was performed to analyze and predict the drug-likeness, molecular and ADME properties of the synthesized molecules.
Assuntos
Anti-Infecciosos , DNA Girase , Antibacterianos/química , Anti-Infecciosos/farmacologia , DNA Girase/metabolismo , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Staphylococcus aureus , Relação Estrutura-Atividade , Tiazóis/química , Tiazóis/farmacologiaRESUMO
The synthesis of 3-[3/4-(2-aryl-2-oxoethoxy)arylidene]chroman/thiochroman-4-one derivatives (1-34) and evaluation of their anticancer activities were aimed in this work. Final compounds were obtained in multistep synthesis reactions using phenol/thiophenol derivatives as starting materials. For anticancer activity evaluation, all compounds were offered to National Cancer Institute (NCI), USA and selected ones were tested against sixty human tumor cell lines derived from nine neoplastic diseases. The activity results were evaluated according to the drug screening protocol of the institute. Compounds containing thiochromanone skeleton exhibited higher anticancer activity.
RESUMO
In this study, we have synthesized 2-[3- or 4-(2-aryl-2-oxoethoxy)arylidene]benzofuran-3-one derivatives (D1-D38) and evaluated their anti-cancer activities. The final compounds were obtained in multistep synthesis reactions using benzofuranon-3-one derivatives (A1-A4, B) as starting materials which were gained in various synthetic ways. Aurone derivatives (C1-C10) were acquired with the condensation reaction of these starting materials and 3-/4-hydroxybenzaldehyde which were then reacted with α-bromoacetophenones to get final compounds. The anti-cancer activity of the selected compounds was performed by National Cancer Institute (NCI), USA against 60 human tumor cell lines derived from nine neoplastic diseases. Compounds exhibited anti-cancer activity in varying ratios.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Benzofuranos/química , Benzofuranos/farmacologia , Antineoplásicos/química , Benzofuranos/síntese química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
The conformational analysis of 6,8-diphenylimidazo[1,2-α]pyrazine molecule (abbreviated as 68DIP) was performed by using B3LYP/6-31G(d) level of theory to find the most stable form. Two staggered stable conformers were observed on the torsional potential energy surface. The equilibrium geometry, bonding features and vibrational frequencies of 68DIP have been investigated by using the DFT (B3LYP) and HF methods for the lowest energy conformer. The first order hyperpolarizability (ß(total)) of this molecular system and related properties (ß, µ, <α> and Δα) are calculated using HF/6-311++G(d,p) and B3LYP/6-311++G(d,p) methods based on the finite-field approach. Stability of the molecule arising from hyperconjugative interactions, charge delocalization and C-Hâ¯N intramolecular hydrogen-bond-like weak interaction has been analyzed using natural bond orbital (NBO) analysis by using B3LYP/6-311++G(d,p) method. The results show that electron density (ED) in the σ* and π* antibonding orbitals and second order delocalization energies E((2)) confirm the occurrence of intramolecular charge transfer (ICT) within the molecule. UV-vis spectrum of the compound was recorded and electronic properties, such as HOMO, LUMO energies, excitation energies and wavelength were performed by TD-DFT/B3LYP, CIS and TD-HF methods by using 6-311++G(d,p) basis set. Finally, the calculation results were applied to simulated infrared spectra of the title compound which show good agreement with observed spectra.
Assuntos
Imidazóis/química , Pirazinas/química , Estabilidade de Medicamentos , Polarização de Fluorescência , Ligação de Hidrogênio , Imidazóis/farmacocinética , Modelos Biológicos , Modelos Moleculares , Conformação Molecular , Simulação de Dinâmica Molecular , Rotação Ocular , Pirazinas/farmacocinética , Teoria Quântica , Espectrofotometria Ultravioleta/métodos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Eletricidade Estática , EstereoisomerismoRESUMO
The syntheses of 1,3-diarylpyrazino[1,2-a]benzimidazole derivatives and the investigation of their anticancer activities were studied. For this, 2-aryloylbenzimidazole derivatives were reacted with 2-bromoacetophenones in acetone to give 1-(2-aryl-2-oxoethyl)-2-aryloylbenzimidazoles. The resulting materials were reacted with ammonium acetate in acetic acid to obtain the aimed compound. In this reaction, microwave irradiation method was applied as the reaction conditions. Anticancer activities of the compounds obtained were investigated. It was observed that some of the compounds showed remarkable anticancer activities.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Benzimidazóis/síntese química , Benzimidazóis/farmacologia , Micro-Ondas , Antineoplásicos/química , Benzimidazóis/química , Linhagem Celular Tumoral , Humanos , Análise EspectralRESUMO
In this study, some 4-(1,5-diarylimidazol-2-yl)thioacetyl-1-phenyl-2,3-dimethyl-3-pyrazoline-5-one derivatives were prepared by reacting 4-(2-chloroacetyl)-1-phenyl-2,3-dimethyl-3-pyrazoline-5-one and 2-mercapto-1, 5-diarylimidazole derivatives. The antinociceptive and anticancer activities of the compounds obtained were investigated. It was observed that some of the compounds, 2a, 2d, 2g, and 2j, showed remarkable antinociceptive activity, and one of the compounds, 2i, showed weak anticancer activity.
Assuntos
Analgésicos/síntese química , Analgésicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Pirazóis/síntese química , Pirazóis/farmacologia , Animais , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Espectrofotometria InfravermelhoRESUMO
Some 1,5-diaryl-3-ethoxycarbonyl-2-methylpyrrole derivatives were obtained by reacting 1-aryl-3-ethoxycarbonylpent-1,4-diones and a suitable aniline derivative or sulfanilamide under Paal-Knorr pyrrole synthesis conditions. The cytotoxicity of the compounds was tested and all compounds, except for compound 2 h, showed a time-dependent increase in cytotoxic activity. Analgesic activities of the compounds were determined by using the tail-flick and tail-immersion methods; some of the compounds showed potent analgesic activity.
Assuntos
Analgésicos , Proliferação de Células/efeitos dos fármacos , Pirróis , Cauda/efeitos dos fármacos , Analgésicos/síntese química , Analgésicos/química , Analgésicos/farmacologia , Animais , Células Cultivadas , Embrião de Mamíferos/citologia , Embrião de Mamíferos/efeitos dos fármacos , Feminino , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Masculino , Camundongos , Pirróis/síntese química , Pirróis/química , Pirróis/farmacologia , RatosRESUMO
In this study, 6-[(4-arylidene-2-phenyl-5-oxoimidazolin-1-yl)phenyl]-4,5-dihydro-3(2H)-pyridazinone and 4-[(4-arylidene-2-phenyl-5-oxoimidazolin-1-yl)phenyl]-1(2H)-phthalazinone derivatives were synthesized by reacting 6-(4-aminophenyl)-4,5-dihydro-3(2H)-pyridazinone or 4-(4-aminophenyl)-1(2H)-phthalazinone compound with different 4-arylidene-2-phenyl-5(4H)-oxazolone derivatives. The vasodilator activities of the compounds were examined both in vitro and in vivo. Some pyridazinone derivatives showed appreciable activity.