RESUMO
Most of pharmaceutical agents display a number of biological activities. It is obvious that testing even one compound for thousands of biological activities is not practically possible. A computer-aided prediction is therefore the method of choice in this case to select the most promising bioassays for particular compounds. Using the PASS Online software, we determined the probable anti-inflammatory action of the 12 new hybrid dithioloquinolinethiones derivatives. Chemical similarity search in the World-Wide Approved Drugs (WWAD) and DrugBank databases did not reveal close structural analogues with the anti-inflammatory action. Experimental testing of anti-inflammatory activity of the synthesized compounds in the carrageenan-induced inflammation mouse model confirmed the computational predictions. The anti-inflammatory activity of the studied compounds (2a, 3a-3k except for 3j) varied between 52.97% and 68.74%, being higher than the reference drug indomethacin (47%). The most active compounds appeared to be 3h (68.74%), 3k (66.91%) and 3b (63.74%) followed by 3e (61.50%). Thus, based on the in silico predictions a novel class of anti-inflammatory agents was discovered.
Assuntos
Anti-Inflamatórios , Carragenina , Relação Quantitativa Estrutura-Atividade , Quinolinas , Animais , Camundongos , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Quinolinas/química , Quinolinas/farmacologia , Inflamação/tratamento farmacológico , Inflamação/induzido quimicamente , Tionas/química , Tionas/farmacologia , Masculino , Edema/tratamento farmacológico , Edema/induzido quimicamenteRESUMO
Most of pharmaceutical agents exhibit several or even many biological activities. It is clear that testing even one compound for thousands of biological activities is a practically not feasible task. Therefore, computer-aided prediction is the method-of-the-choice to select the most promising bioassays for particular compounds. Using PASS Online software, we determined the likely anti-inflammatory action of the 13 dithioloquinolinethione derivatives with antimicrobial activities. Chemical similarity search in the Cortellis Drug Discovery Intelligence database did not reveal close structural analogues with anti-inflammatory action. Experimental testing of anti-inflammatory activity of the synthesized compounds in carrageenan-induced inflammation mouse model confirmed the computational predictions. The anti-inflammatory activity of the studied compounds was comparable with or higher than the reference drug Indomethacin. Thus, based on the in silico predictions, novel class of the anti-inflammatory agents was discovered.
