RESUMO
(E)-3-(2-Benzylidenehydrazinyl)-5,6-diphenyl-1,2,4-triazines analogs 1-27 were synthesized by multi-step reaction scheme and subjected to in vitro inhibitory screening against α-amylase and α-glucosidase enzymes. Out of these twenty-seven synthetic analogs, ten compounds 14-17, 19, and 21-25 are structurally new. All compounds exhibited good to moderate inhibitory potential in terms of IC50 values ranging (IC50 = 13.02 ± 0.04-46.90 ± 0.05 µM) and (IC50 = 13.09 ± 0.08-46.44 ± 0.24 µM) in comparison to standard acarbose (IC50 = 12.94 ± 0.27 µM and 10.95 ± 0.08 µM), for α-amylase and α-glucosidase, respectively. Structure-activity relationship indicated that analogs with halogen substitution(s) were found more active as compared to compounds bearing other substituents. Kinetic studies on most active α-amylase and α-glucosidase inhibitors 5, 7, 9, 15, 24, and 27, suggested non-competitive and competitive types of inhibition mechanism for α-amylase and α-glucosidase, respectively. Molecular docking studies predicted the good protein-ligand interaction (PLI) profile with key interactions such as arene-arene, H-<, <-<, and <-H etc., against the corresponding targets.
Assuntos
Acarbose/uso terapêutico , Diabetes Mellitus Tipo 2/dietoterapia , Simulação de Acoplamento Molecular/métodos , Triazinas/química , alfa-Amilases/antagonistas & inibidores , alfa-Glucosidases/química , Humanos , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Despite of a diverse range of biological activities associated with chalcones and bis-chalcones, they are still neglected by the medicinal chemist for their possible α-amylase inhibitory activity. So, the current study is based on the evaluation of this class for the identification of new leads as α-amylase inhibitors. For that purpose, a library of substituted chalcones 1-13 and bis-chalcones 14-18 were synthesized and characterized by spectroscopic techniques EI-MS and 1H NMR. CHN analysis was carried out and found in agreement with the calculated values. All compounds were evaluated for in vitro α-amylase inhibitory activity and demonstrated good activities in the range of IC50â¯=â¯1.25⯱â¯1.05-2.40⯱â¯0.09⯵M as compared to the standard acarbose (IC50â¯=â¯1.04⯱â¯0.3⯵M). Limited structure-activity relationship (SAR) was established by considering the effect of different groups attached to aryl rings on varying inhibitory activity. SMe group in chalcones and OMe group in bis-chalcones were found more influential on the activity than other groups. However, in order to predict the involvement of different groups in the binding interactions with the active site of α-amylase enzyme, in silico studies were also conducted.
Assuntos
Chalconas/farmacologia , Inibidores Enzimáticos/farmacologia , alfa-Amilases/antagonistas & inibidores , Chalconas/síntese química , Chalconas/química , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-Atividade , alfa-Amilases/metabolismoRESUMO
Current research is based on the identification of novel inhibitors of α-amylase enzyme. For that purpose, new hybrid molecules of hydrazinyl thiazole substituted chromones 5-27 were synthesized by multi-step reaction and fully characterized by various spectroscopic techniques such as EI-MS, HREI-MS, 1H-NMR and 13C-NMR. Stereochemistry of the iminic bond was confirmed by NOESY analysis of a representative molecule. All compounds 5-27 along with their intervening intermediates 1-4, were screened for in vitro α-amylase inhibitory, DPPH and ABTS radical scavenging activities. All compounds showed good inhibition potential in the range of IC50 = 2.186-3.405 µM as compared to standard acarbose having IC50 value of 1.9 ± 0.07 µM. It is worth mentioning that compounds were also demonstrated good DPPH (IC50 = 0.09-2.233 µM) and ABTS (IC50 = 0.584-3.738 µM) radical scavenging activities as compared to standard ascorbic acid having IC50 = 0.33 ± 0.18 µM for DPPH and IC50 = 0.53 ± 0.3 µM for ABTS radical scavenging activities. In addition to that cytotoxicity of the compounds were checked on NIH-3T3 mouse fibroblast cell line and found to be non-toxic. In silico studies were performed to rationalize the binding mode of compounds (ligands) with the active site of α-amylase enzyme.
Assuntos
Cromonas/farmacologia , Inibidores Enzimáticos/farmacologia , Sequestradores de Radicais Livres/farmacologia , alfa-Amilases/antagonistas & inibidores , Animais , Compostos de Bifenilo , Cromonas/química , Simulação por Computador , Avaliação Pré-Clínica de Medicamentos/métodos , Inibidores Enzimáticos/química , Sequestradores de Radicais Livres/química , Espectrometria de Massas , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Células NIH 3T3 , Picratos , Relação Estrutura-Atividade , Tiazóis/químicaRESUMO
7-Hydroxy-4-methyl-2H-chromen-2-one (2), 7-hydroxy-4,5-dimethyl-2H-chromen-2-one (15) and their some derivatives were synthesized for exploring selected biological screening. The compounds 9 and 13 had shown high degree of cytotoxic activity. Three compound 9, 10 and 13 showed high degree of bactericidal activity amongst the present series.
Assuntos
Antibacterianos/farmacologia , Benzopiranos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Fitoterapia , Animais , Antibacterianos/administração & dosagem , Antibacterianos/síntese química , Antibacterianos/uso terapêutico , Artemia/efeitos dos fármacos , Benzopiranos/administração & dosagem , Benzopiranos/síntese química , Benzopiranos/uso terapêutico , Humanos , Dose Letal Mediana , Testes de Sensibilidade MicrobianaRESUMO
Three glycosides and a long chain alcohol were isolated from the bulbs of Polianthes tuberosa, these were identified as 3,29-dihydroxystigmast-5-ene-3-O-beta-D-galactopyranoside (1), ethyl beta-D-galactopyranoside (2), ethyl-alpha-D-galactopyranoside (3), and 1-tricosanol (4). The structures were determined by extensive spectroscopic and chemical methods. All four isolated compounds were screened for their cytotoxicity, antibacterial and antifungal activities, none of the compounds showed any significant activity.