RESUMO
In recent studies, monoamine oxidase (MAO) inhibitory effects of various thiazolylhydrazone derivatives have been demonstrated. Within the scope of this study, 12 new compounds containing thiazolylhydrazone groups were synthesized. The structures of the obtained compounds were elucidated by 1H NMR, 13C NMR, and high-resolution mass spectrometry (HRMS) methods. The inhibitory effects of the final compounds on MAO enzymes were investigated by means of in vitro methods. In addition to enzyme inhibition studies, enzyme kinetic studies of compounds with high inhibitory activity were examined, and their effects on substrate-enzyme relations were investigated. Additionaly, cytotoxicity tests were carried out to determine the toxicities of the selected compounds, and the compounds were found to be nontoxic. The interactions of the active compound with the active site of the enzyme were characterized by in silico methods.
RESUMO
This study delves into the intricate dynamics of the inflammatory response, unraveling the pivotal role played by cyclooxygenase (COX) enzymes, particularly COX-1 and COX-2 subtypes. Motivated by the pursuit of advancing scientific knowledge, our contribution to this field is marked by the design and synthesis of novel pyrrole derivatives. Crafted as potential inhibitors of COX-1 and COX-2 enzymes, our goal was to unearth molecules with heightened efficacy in modulating enzyme activity. A meticulous exploration of a synthesis library, housing around 3000 compounds, expedited the identification of potent candidates. Employing advanced docking studies and field-based Quantitative Structure-Activity Relationship (FB-QSAR) analyses enriched our understanding of the complex interactions between synthesized compounds and COX enzymes. Guided by FB-QSAR insights, our synthesis path led to the identification of compounds 4g, 4h, 4l, and 4k as potent COX-2 inhibitors, surpassing COX-1 efficacy. Conversely, compounds 5b and 5e exhibited heightened inhibitory activity against COX-1 relative to COX-2. The utilization of pyrrole derivatives as COX enzyme inhibitors holds promise for groundbreaking advancements in the domain of anti-inflammatory therapeutics, presenting avenues for innovative pharmaceutical exploration.
RESUMO
Aim: Design of 5-methoxy benzofuran hybrids with 2-carbohydrazide and 2-(1,3,4-oxadiazol-2-yl) as potential inhibitors of monoamine oxidase (MAO)-B targeting Parkinson disease. Materials and methods: 12 compounds were synthesized and analyzed via high-resolution mass spectrometry, 1H nuclear magnetic resonance and 13C nuclear magnetic resonance techniques. In vitro fluorometric assay was used to investigate the activity of the synthesized compounds on both MAO-A and MAO-B isozymes. Results: Three compounds - 3a, 3c and 3e - displayed half maximal inhibitory concentration values of 0.051 ± 0.002, 0.038 ± 0.001 and 0.077 ± 0.003 µM in the inhibition of MAO-A and 0.048 ± 0.002, 0.040 ± 0.001 and 0.072 ± 0.002 µM for MAO-B, respectively. A molecular dynamics simulation study showed that compound 3c has poor stability as a complex with MAO-A. Conclusion: Compound 3c may be a potential candidate for the treatment of Parkinson disease.
Assuntos
Monoaminoxidase , Doença de Parkinson , Humanos , Monoaminoxidase/metabolismo , Inibidores da Monoaminoxidase/farmacologia , Inibidores da Monoaminoxidase/química , Doença de Parkinson/tratamento farmacológico , Simulação de Acoplamento Molecular , Espectrometria de Massas , Relação Estrutura-Atividade , Estrutura MolecularRESUMO
The use of dual acetylcholinesterase (AChE)-monoamine oxidase B (MAO-B) inhibitors is a new approach in the treatment of Alzheimer disease (AD). In this work, 14 new benzothiazoles (4a-4n) were designed and synthesized. In biological activity studies, the AChE, butyrylcholinesterase (BChE), MAO-A and MAO-B inhibitory potentials of all compounds were evaluated using the in vitro fluorometric method. Additionally, amyloid beta (Aß)-aggregation inhibitory effects of active compounds were evaluated by means of an in vitro kit-based method. The biological evaluation showed that compounds 4a, 4d, 4f, 4h, 4k and 4m displayed significant activity against AChE and MAO-B enzymes. Compound 4f displayed inhibitory activity against AChE and MAO-B enzyme with IC50 values of 23.4 ± 1.1 nM and 40.3 ± 1.7 nM, respectively. It has been revealed that compound 4f may have the potential to inhibit AChE and MAO-B enzymes, as well as the ability to prevent the formation of beta amyloid plaques accumulated in the brains of patients suffering from AD. In silico studies also support the obtained biological activity findings. Compound 4f provided strong interactions with the active site of both enzymes. In particular, the interaction of compound 4f with flavin adenine dinucleotide (FAD) in the MAO-B enzyme active site is a promising and exciting finding.
RESUMO
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
In this study, some aryl [3-(imidazol-1-yl/triazol-1-ylmethyl)benzofuran-2-yl] ketones, aryl (3-methyl-benzofuran-2-yl) ketoximes and aryl [3-(imidazol-1-yl/triazol-1-ylmethyl)benzofuran-2-yl] ketoximes were synthesised starting from 2-aryloyl-3-methyl-benzofuranes. The structure elucidation of the compounds was performed by IR, 1H-NMR, MASS spectroscopy and elemental analyses. Antifungal activities of the compounds were examined and moderate activity was obtained.
Assuntos
Antifúngicos/síntese química , Antifúngicos/farmacologia , Azóis/química , Benzofuranos/química , Imidazóis/química , Oximas/química , Oximas/farmacologia , Antifúngicos/química , Candida/efeitos dos fármacos , Metilação , Estrutura Molecular , Oximas/síntese química , Relação Estrutura-AtividadeRESUMO
In this study, some new nitroimidazole derivatives were obtained from 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethylamine dihydrochloride (4) and 1-(2-bromoethyl)-2-methyl-5-nitroimidazole (5), which were prepared using metronidazole. Compound 4 was reacted with arylisothiocyanates (6) to obtain 1-[2-(2-methyl-5-nitroimidazol-1-yl)ethyl]-3-arylthioureas (7) and the latter with alpha-bromoacetophenones (8) to give 3-[2-(2-methyl-5-nitroimidazol-1-yl)ethyl]-2-arylimino-4-aryl-4-thiazolines (9). Also 1-[2-(2-methyl-5-nitroimidazol-1-yl)ethyl]-2-phenyl-4-arylideneimidazolin-5-ones (11) were prepared by reaction of 4 with 2-phenyl-4-arylidene-5-oxazolones (10). The reaction of the other starting material 5 with 5-arylidenethiazolidin-2,4-dione (12) gave 3-[2-(2-methyl-5-nitroimidazol-1-yl)ethyl]-5-arylidenethiazolidin-2,4-dione (13) derivatives. Structural elucidation of the compounds was performed by IR, 1H-NMR and MASS spectroscopic data and elemental analysis results. Antimicrobial activities of the compounds were examined and moderate activity was obtained.
Assuntos
Antibacterianos/síntese química , Antifúngicos/síntese química , Nitroimidazóis/síntese química , Nitroimidazóis/farmacologia , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Fungos/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Raios Infravermelhos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Metronidazol/química , Testes de Sensibilidade MicrobianaRESUMO
In this study, some aryl (3-methyl-benzofuran-2-yl) ketoximes and their ethers and esters were synthesised. The structure elucidation of the compounds was performed by IR, 1H-NMR, MASS spectroscopy and elemental analyses. Antifungal activities of the compounds were examined and moderate activity was obtained.
Assuntos
Antifúngicos/síntese química , Benzofuranos/síntese química , Oximas/síntese química , Antifúngicos/farmacologia , Benzofuranos/farmacologia , Testes de Sensibilidade Microbiana/estatística & dados numéricos , Oximas/farmacologiaRESUMO
In this study, some aryl(benzofuran-2-yl)ketoximes and their ethers and esters were synthesised. The structure elucidation of the compounds was performed by IR, 1H NMR and mass spectroscopic data and elemental analyses results. Antifungal activities of the compounds were examined and notable activity was obtained.