Computer-aided discovery of pleiotropic effects: Anti-inflammatory action of dithioloquinolinethiones as a case study

• Published in: SAR and QSAR in environmental research Vol. 33; no. 4; pp. 273 - 287
• Main Authors: Medvedeva, S.M., Shikhaliev, K.S., Geronikaki, A.A., Savosina, P.I., Druzhilovskiy, D.S., Poroikov, V.V.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 03-04-2022
• Subjects: Animals; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; antimicrobial action; bioactivity profiles prediction in silico; Carrageenan - therapeutic use; Carrageenan - toxicity; carrageenan-induced inflammation model; Computers; Dithioloquinolinethiones; Edema - chemically induced; Edema - drug therapy; Mice; novel anti-inflammatory agents; PASS online; Quantitative Structure-Activity Relationship; Structure-Activity Relationship; novel anti-inflammatory agents; PASS online; Dithioloquinolinethiones; bioactivity profiles prediction in silico; carrageenan-induced inflammation model; antimicrobial action
• ISSN: 1062-936X; 1029-046X
• DOI: 10.1080/1062936X.2022.2064547

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.