RESUMO
BACKGROUND: We have developed a new series of 36 substituted thiazole derivatives prepared via reaction of substituted benzothiazole-2-amine with substituted phenacyl bromide. OBJECTIVE: This study was aimed to develop and successfully evaluate anti-inflammatory activity of substituted thiazole derivatives. METHOD: A new series of 36 substituted thiazole derivatives was synthesized and derivatives were characterized by analytical and spectrometric methods like IR, MS, and 1H NMR. The molecular docking was performed for all the synthesized thiazole derivatives to assess their binding affinities to COX-2 isozyme. The best compounds from docking study were subjected for their anti-inflammatory activity by using rat hind paw edema method. RESULTS: Results from carrageenan-induced hind paw edema showed that compounds 3h, 5a, 5e, 9d, and 9h possess significant anti-inflammatory activity. The result from vascular permeability indicating inhibition of vascular permeability with compounds 3h and 9h is significant and results from cotton pellet granuloma formation models show greater degree of inhibition with compounds 3h and 5a to contribute to their significant anti-inflammatory activity. CONCLUSION: This study provides successful development of novel thiazole derivatives. Their binding affinities to COX-2 enzyme were also confirmed, indicating that developed molecules are comparable to diclofenac and hence could be promising anti-inflammatory agents.
Assuntos
Acetofenonas/síntese química , Anti-Inflamatórios/síntese química , Edema/tratamento farmacológico , Compostos Heterocíclicos/síntese química , Tiazóis/síntese química , Animais , Anti-Inflamatórios/farmacologia , Permeabilidade Capilar/efeitos dos fármacos , Carragenina , Ciclo-Oxigenase 2/metabolismo , Desenho de Fármacos , Descoberta de Drogas , Edema/induzido quimicamente , Compostos Heterocíclicos/uso terapêutico , Humanos , Camundongos , Ligação Proteica , Ratos , Ratos Wistar , Relação Estrutura-Atividade , Tiazóis/uso terapêuticoRESUMO
Fragment based Quantitative structure activity relationship (QSAR) analysis on reported 25 2-(2-(4-aryloxybenzylidene) hydrazinyl) benzothiazole dataset as antitubercular agents were carried out. Molecules in the current dataset were fragmented into six fragments (R1, R2, R3, R4, R5, R6).Group based QSAR Models were derived using Multiple linear regression (MLR) analysis and selected on the basis of various statistical parameters. Dataset of benzothiazole reveled importance of presence of halogen atoms on is essential requirement. The generated models will provide structural requirements of benzothiazole derivatives which can be used to design and develop potent antitubercular derivatives.
