ABSTRACT
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.
Subject(s)
Anti-Inflammatory Agents , Carrageenan , Quantitative Structure-Activity Relationship , Quinolines , Animals , Mice , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Quinolines/chemistry , Quinolines/pharmacology , Inflammation/drug therapy , Inflammation/chemically induced , Thiones/chemistry , Thiones/pharmacology , Male , Edema/drug therapy , Edema/chemically inducedABSTRACT
Searching for novel compounds with antibiotic activity and understanding their mechanism of action is extremely important. The ribosome is one of the main targets for antibiotics in bacterial cells. Even if the molecule does not suit the clinical application for whatever reasons, an investigation of its mechanism of action can deepen our understanding of the ribosome function. Such data can inform us on how the already used translational inhibitors can be modified. In this study, we demonstrate that 1-(2-oxo-2-((4-phenoxyphenyl).
ABSTRACT
A comparative study of kinetics and mechanisms of action of some photodynamic herbicides (dipyridil, phenantroline, and acepox) on mechanical resistance and acetylcholinesterase activity of erythrocytes has been carried out. Acepox had a slight damaging effect, and phenantroline was the strongest inhibitor. The data on mechanical destruction of erythrocytes correlated with tests on toxicity of obtained samples carried out on mice and infusorians. The proposed criteria may help to search for nontoxic drugs.
